Methods to modulate in VIVO levels of hydrogen sulfide by engineered organisms

Abstract

Provided are microorganisms, systems and methods for modulating H2S. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of consuming H2S, converting H2S to L-cysteine, L-cysteine to glutathione, or to persulfides, polysulfides, or sulfur clusters. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of producing H2S, degrading glutathione to L-cysteine and H2S, or reducing sulfite to H2S. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of sensing environmental cues associated with a disease states and turning on H2S consumption pathways.

Description

[0001]Attorney Docket No.: NEX-16225 METHODS TO MODULATE IN VIVO LEVELS OF HYDROGEN SULFIDE BY ENGINEERED ORGANISMS RELATED APPLICATIONS This application claims the benefit of priority to U.S. Patent Application serial number 63 / 541,467, filed September 29, 2023; which is incorporated by reference in its entirety. GOVERNMENT SUPPORT This invention was made with government support under Grant Number R21EB033892 awarded by the National Institutes of Health and under Grant Number 1938052 awarded by National Science Foundation. The Government has certain rights in the invention. BACKGROUND In the last decade, the use of engineered probiotics has emerged as a promising therapeutic strategy for gastrointestinal diseases such as Chron’s disease, colorectal cancer, and genetic disorders. The technology relies on the engineered microbe that can perform non- native functions of the human body including consumption of toxic metabolites, promoting anti-tumor activity, and modifying host gene expression. Advancements in metagenomics and metabolomics of the human gut microbiome have identified candidate metabolites associated with gastrointestinal diseases, such as hydrogen sulfide (H2S). Experiments in vitro and in animals suggest that H2S exerts its effects in a dose-dependent manner. H2S’s role as a therapeutic or toxic mediator in disease is contradictory, and appears to depend on concentration, disease target, and the route of administration. H2S-based pharmaceutical drugs for gastrointestinal pain and inflammatory bowel disease (IBD) is being developed and engineered microbes as therapeutics for metabolic disorders such as phenylketonuria (PKU) are being developed. Despite the promise of microbial and H2S-based therapeutics, there remains a significant technical challenge in modifying H2S levels in the human intestinal environment due to its volatility. There are currently no metabolite controllers for H2S. Overcoming this challenge could enable a dramatic expansion in the disease target portfolio and could serve as a platform for modulating other intestinal metabolites of interest. Accordingly, there is need for methods for modifying H2S levels in the human intestinal environment. 1 FH12512877.6 Attorney Docket No.: NEX-16225 SUMMARY OF THE INVENTION Bacteria (smart probiotics) were engineered to modify the intestinal environment for applications in diseases such as inflammatory bowel disease (IBD). The smart probiotics produce or consume intestinal metabolites to treat disease, and in some embodiments sense chemical markers to identify disease and respond accordingly. Specifically, the smart probiotics modify hydrogen sulfide ('H2S' or 'sulfide') in the human intestine. Described is a set of microbes that modify sulfur species in the gut. A dynamic microbial controller for intestinal sulfur species, specifically H2S, has never been developed. In one aspect the present disclosure provides an engineered microorganism, comprising a first gene encoding a serine acetyltransferase; and a second gene encoding a cysteine synthase A. In some embodiments, the serine acetyltransferase has reduced L- cysteine feedback inhibition as compared to a wild-type serine acetyltransferase from the same bacterial subtype under the same conditions. In some embodiments, the serine acetyltransferase is mutated at positions 167 and / or 256. In some embodiments, the serine acetyltransferase comprises the amino acid sequence set forth in SEQ ID NO: 1 or 2. In some embodiments, the first gene is a CysE gene. In some embodiments, the CysE gene comprises the nucleic acid sequence set forth in SEQ ID NO: 2 or 4. In some embodiments, the cysteine synthase A comprises the amino acid sequence set forth in SEQ ID NO: 5. In some embodiments, the second gene is a CysK gene. In some embodiments, the CysK gene comprises the nucleic acid sequence set forth in SEQ ID NO: 6. In some embodiments, the engineered microorganism converts H2S to L-cysteine. In some embodiments, the engineered microorganism further comprises a third gene encoding a glutathione biosynthesis bifunctional protein or encoding a glutamate-cysteine ligase (ghsA) and a glutathione synthase (gshB). In some embodiments, the third gene encodes the glutathione biosynthesis bifunctional protein. In some embodiments, the glutathione biosynthesis bifunctional protein comprises the amino acid sequence set forth in SEQ ID NO: 7 or 9. In some embodiments, the third gene is a gshF (gshAB) gene. In some embodiments, the gshF gene comprises the nucleic acid sequence set forth in SEQ ID NO: 8 or 10. In some embodiments, the third gene encodes the glutamate-cysteine ligase and the glutathione synthase. In some embodiments, the glutamate-cysteine ligase comprises the amino acid sequence set forth in SEQ ID NO: 11. In some embodiments, the glutathione synthase comprises the amino acid sequence set forth in SEQ ID NO: 13. In some embodiments, the third gene comprises a gshA gene and a gshB gene. In some embodiments, 2 FH12512877.6 Attorney Docket No.: NEX-16225 the gshA gene comprises the nucleic acid sequence set forth in SEQ ID NO: 12. In some embodiments, the gshB gene comprises the nucleic acid sequence set forth in SEQ ID NO: 14. In some embodiments, the engineered microorganism converts H2S to L-cysteine, converts L-cysteine to gamma-L-glutamyl-L-cysteine, and converts gamma-L-glutamyl-L- cysteine to glutathione. In some embodiments, the engineered microorganism lacks native decR (DNA- binding transcriptional activator), iscS (cysteine desulfurase), yhaM (L-cysteine desulfidase) and / or yhaO (L-cysteine importer). In some embodiments, the decR comprises the amino acid sequence set forth in SEQ ID NO: 37 or encoded by the nucleic acid set forth in SEQ ID NO: 38. In some embodiments, the iscS comprises the amino acid sequence set forth in SEQ ID NO: 35 or encoded by the nucleic acid set forth in SEQ ID NO: 36. In some embodiments, the yhaM comprises the amino acid sequence set forth in SEQ ID NO: 25 or encoded by the nucleic acid set forth in SEQ ID NO: 26. In some embodiments, the yhaO comprises the amino acid sequence set forth in SEQ ID NO: 27 or encoded by the nucleic acid set forth in SEQ ID NO: 28. In some embodiments, the first gene, the second gene, the third gene, and / or the fourth gene is a heterologous or homologous gene. In some embodiments, In some embodiments, the first gene, the second gene, and / or the third gene is operably linked to a promoter that is activated or repressed by an environmental cue. In some embodiments, the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL). In some embodiments, the promoter is a ROS-activated promoter. In some embodiments, the ROS-activated promoter is a oxyS promoter is an ROS-activated promoter. In some embodiments, the oxyS promoter is from E. coli. In some embodiments, the engineered microorganism expresses a transcription factor OyxR. In some embodiments, ROS activates the OxyR, which activates the native OxyS promoter from E. coli. In some embodiments, the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO: 41. In some embodiments, the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO: 40. In some embodiments the promoter is a luminal H2S-activated promoter. In some embodiments, the luminal H2S-activated promoter is an IR9 promoter. In some embodiments, the IR9 promoter is from B. licheniformis. In some embodiments, the engineered microorganism expresses NreB and NreC. In some embodiments, the NreB and NreC are from B. licheniformis. In some embodiments, the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter. In some embodiments, the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 46. In some embodiments, the NreB 3 FH12512877.6 Attorney Docket No.: NEX-16225 comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO: 43. In some embodiments, the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO: 45. In some embodiments, the promoter is a thiosulfate-activated promoter. In some embodiments, the thiosulfate-activated promoter is a phsA342 promoter. In some embodiments, the phsA342 promoter is from S. halifaxensis. In some embodiments, the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor. In some embodiments, the thiosulfate sensor is thsS. In some embodiments, the transcription factor is thsR. In some embodiments, the thsR from S. halifaxensis. In some embodiments, the activated transcription factor, thsR, activates the promoter phsA342. In some embodiments, the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 51. In some embodiments, the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO: 48. In some embodiments, the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or encoded by the nucleic acid set forth in SEQ ID NO: 50. In some embodiments, the promoter is an interleukin- or pro-inflammatory protein-activated promoter. In some embodiments, the Interleukin (IL) is IL-1, IL-4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C- X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1. In some embodiments, the engineered microorganism expresses a transcription factor which is activated by an Interleukin or a pro-inflammatory protein. In some embodiments, the activated transcription factor activates the promoter. In some embodiments, the engineered microorganism expresses a sulfide quinone reductase (SQR) enzyme. In some embodiments, sulfide quinone reductase (SQR) enzyme is from Rhodobacter Capsulatus or Wolinella succinogenes. In some embodiments, the sulfide quinone reductase (SQR) enzyme comprises the amino acid sequence set forth in SEQ ID NO: 15 or 17 or encoded by the nucleic acid set forth in SEQ ID NO: 16 or 18. In some embodiments, the engineered microorganism is a bacterium. In some embodiments, the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium. In some embodiments, the bacterium is Escherichia coli strain Nissle, MG1655, or S1030. In some embodiments, the bacterium is an auxotroph 4 FH12512877.6 Attorney Docket No.: NEX-16225 in a gene that is important for cellular growth. In some embodiments, the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof. In some embodiments, the bacterium comprises a kill switch. In one aspect the present disclosure provides a pharmaceutically acceptable composition comprising the microorganism described herein; and a pharmaceutically acceptable carrier. In some embodiments, the composition is formulated for oral or rectal administration. In one aspect the present disclosure provides an engineered microorganism, comprising a first gene encoding a desulfidase. In some embodiments, the desulfidase comprises the amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the first gene is a yhaM gene. In some embodiments, the yhaM gene comprises the nucleic acid sequence set forth in SEQ ID NO: 26. In some embodiments, the engineered microorganism converts L-cysteine to H2S. In some embodiments, the engineered microorganism further comprises a second gene encoding a peptidase T, a third gene encoding a glutathione hydrolase, and a fourth gene encoding an aminopeptidase B. In some embodiments, the peptidase T comprises the amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the second gene is a pepT gene. In some embodiments, the pepT gene comprises the nucleic acid sequence set forth in SEQ ID NO: 20. In some embodiments, the glutathione hydrolase comprises the amino acid sequence set forth in SEQ ID NO: 23. In some embodiments, the third gene is a ggt gene. In some embodiments, the ggt gene comprises the nucleic acid sequence set forth in SEQ ID NO: 24. In some embodiments, the aminopeptidase B comprises the amino acid sequence set forth in SEQ ID NO: 21. In some embodiments, the fourth gene is a pepB gene. In some embodiments, the pepB gene comprises the nucleic acid sequence set forth in SEQ ID NO: 22. In some embodiments, the engineered microorganism converts glutathione to L- Cysteinylglycine, L-Cysteinylglycine to L-cysteine, and L-cysteine to H2S. In some embodiments, In some embodiments, the engineered microorganism further comprises a fifth gene encoding a L-cysteine importer. In some embodiments, the L-cysteine importer comprises the amino acid sequence set forth in SEQ ID NO: 27. In some embodiments, the fifth gene is a yhaO gene. In some embodiments, the yhaO gene comprises the nucleic acid sequence set forth in SEQ ID NO: 28. In some embodiments, the first gene, the second gene, the third gene, the fourth gene, and / or the fifth gene is a heterologous or homologous gene. 5 FH12512877.6 Attorney Docket No.: NEX-16225 In some embodiments, the first gene, the second gene, the third gene, the fourth gene, and / or the fifth gene is operably linked to a promoter that is activated or repressed by an environmental cue. In some embodiments, the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL). In some embodiments, the promoter is a ROS-activated promoter. In some embodiments the ROS- activated promoter is a oxyS promoter is an ROS-activated promoter. In some embodiments, the oxyS promoter is from E. coli. In some embodiments the engineered microorganism expresses a transcription factor OyxR. In some embodiments, ROS activates the OxyR, which activates the native OxyS promoter from E. coli. In some embodiments, the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO: 41. In some embodiments, the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO: 40. In some embodiments, the promoter is a luminal H2S-activated promoter. In some embodiments, the luminal H2S-activated promoter is an IR9 promoter. In some embodiments the IR9 promoter is from B. licheniformis. In some embodiments, the engineered microorganism expresses NreB and NreC. In some embodiments, the NreB and NreC are from B. licheniformis. In some embodiments, the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter. In some embodiments, the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 46. In some embodiments, the NreB comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO: 43. In some embodiments, the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO: 45. In some embodiments, the promoter is a thiosulfate- activated promoter. In some embodiments, the thiosulfate-activated promoter is a phsA342 promoter. In some embodiments, the phsA342 promoter is from S. halifaxensis. In some embodiments, the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor. In some embodiments, the thiosulfate sensor is thsS. In some embodiments, the transcription factor is thsR. In some embodiments, the thsR from S. halifaxensis. In some embodiments, the activated transcription factor, thsR, activates the promoter phsA342. In some embodiments, the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 51. In some embodiments, the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO: 48. In some embodiments, In some embodiments, the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or encoded by the nucleic acid set forth in SEQ ID NO: 50. In some embodiments, the promoter is an interleukin- or a pro-inflammatory protein- 6 FH12512877.6 Attorney Docket No.: NEX-16225 activated promoter. In some embodiments, the Interleukin (IL) is IL-1, IL-4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C- reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1. In some embodiments, the engineered microorganism expresses a transcription factor which is activated by an interleukin or a pro-inflammatory protein. In some embodiments, the activated transcription factor activates the promoter. In some embodiments, the engineered microorganism is a bacterium. In some embodiments, the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium. In some embodiments, the bacterium is Escherichia coli strain Nissle, MG1655, or S1030. In some embodiments, the bacterium is an auxotroph in a gene that is important for cellular growth. In some embodiments, the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof. In some embodiments, the bacterium comprises a kill switch. In one aspect the present disclosure provides a pharmaceutically acceptable composition comprising the microorganism disclosed herein; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable composition is formulated for oral or rectal administration. In one aspect the present disclosure provides an engineered microorganism comprising a first gene and a second gene encoding two subunits of a sulfite reductase. In some embodiments, the sulfite reductase comprises the amino acid sequence set forth in SEQ ID NO: 29 or 31. In some embodiments, the first gene is a CysI gene and the second gene is a CysJ gene. In some embodiments, the CysI gene comprises the nucleic acid sequence set forth in SEQ ID NO: 30. In some embodiments, the CysJ gene comprises the nucleic acid sequence set forth in SEQ ID NO: 32. In some embodiments, In some embodiments, the engineered microorganism disclosed herein further comprises a third gene encoding a siroheme synthetase. In some embodiments, the siroheme synthetase comprises the amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the third gene is a CysG gene. In some embodiments, the CysG gene comprises the nucleic acid sequence set forth in SEQ ID NO: 34. In some embodiments, the 7 FH12512877.6 Attorney Docket No.: NEX-16225 engineered microorganism converts sulfite to H2S. In some embodiments, the first gene, the second gene, and / or the third gene is a heterologous or homologous gene. In some embodiments, the first gene, the second gene, and / or the third gene is operably linked to a promoter that is activated or repressed by an environmental cue. In some embodiments the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL). In some embodiments, the promoter is a ROS-activated promoter. In some embodiments the ROS-activated promoter is a oxyS promoter is an ROS-activated promoter. In some embodiments, the oxyS promoter is from E. coli. In some embodiments, the engineered microorganism expresses a transcription factor OyxR. In some embodiments, ROS activates the OxyR, which activates the native OxyS promoter from E. coli. In some embodiments, the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO: 41. In some embodiments, the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO: 40. In some embodiments, the promoter is a luminal H2S-activated promoter. In some embodiments, the luminal H2S-activated promoter is an IR9 promoter. In some embodiments, the IR9 promoter is from B. licheniformis. In some embodiments, the engineered microorganism expresses NreB and NreC. In some embodiments, the NreB and NreC are from B. licheniformis. In some embodiments, the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter. In some embodiments, the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 46. In some embodiments, the NreB comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO: 43. In some embodiments, the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO: 45. In some embodiments, the promoter is a thiosulfate-activated promoter. In some embodiments, the thiosulfate-activated promoter is a phsA342 promoter. In some embodiments, the phsA342 promoter is from S. halifaxensis. In some embodiments, the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor. In some embodiments, the thiosulfate sensor is thsS. In some embodiments, the transcription factor is thsR. In some embodiments, the thsR from S. halifaxensis. In some embodiments, the activated transcription factor, thsR, activates the promoter phsA342. In some embodiments, the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO: 51. In some embodiments, the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO: 48. In some embodiments, the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or 8 FH12512877.6 Attorney Docket No.: NEX-16225 encoded by the nucleic acid set forth in SEQ ID NO: 50. In some embodiments, the promoter is an interleukin- or a pro-inflammatory protein-activated promoter. In some embodiments, the Interleukin (IL) is IL-1, IL-4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL- 27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1. In some embodiments, the engineered microorganism expresses a transcription factor which is activated by an interleukin or a pro-inflammatory protein. In some embodiments, the activated transcription factor activates the promoter. In some embodiments, the engineered microorganism is a bacterium. In some embodiments, the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium. In some embodiments, the bacterium is Escherichia coli strain Nissle, MG1655, or S1030. In some embodiments, the bacterium is an auxotroph in a gene that is important for cellular growth. In some embodiments, the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof. In some embodiments, the bacterium comprises a kill switch. In one aspect the present disclosure provides a pharmaceutically acceptable composition comprising the microorganism disclosed herein; and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable composition is formulated for oral or rectal administration. In one aspect the present disclosure provides a method of treating a disease associated with increased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism disclosed herein or the pharmaceutically acceptable composition disclosed herein. In some embodiments, the disease associated with increased H2S levels is a neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), an ulcer, colorectal cancer, mental retardation, Down Syndrome, intestinal pain, H2S poisoning, an inflammatory disease, a cardiometabolic disease, Ethylmalonic encephalopathy, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer's 9 FH12512877.6 Attorney Docket No.: NEX-16225 disease, Parkinson's disease, Huntington's disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus. In one aspect the present disclosure provides a method of treating a disease associated with decreased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism disclosed herein or the pharmaceutically acceptable composition disclosed herein. In some embodiments, the disease associated with decreased H2S levels neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, an ulcer, colorectal cancer, intestinal pain, an inflammatory disease, a cardiometabolic disease, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer's disease, Parkinson’s disease, Huntington’s disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus. In one aspect the present disclosure provides a method of reducing H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism disclosed herein or the pharmaceutically acceptable composition disclosed herein. In one aspect the present disclosure provides a method of increasing H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism disclosed herein or the pharmaceutically acceptable composition disclosed herein. In one aspect the present disclosure provides a method of modulating H2S levels based on an environmental cue comprising administering to a subject in need thereof an effective amount of the engineered microorganism disclosed herein. In one aspect the present disclosure provides a method of reducing H2S levels in environmental water or wastewater, comprising administering thereof an effective amount of the engineered microorganism described herein. BRIEF DESCRIPTION OF THE DRAWINGS Fig.1 shows that H2S affects various physiological processes in the gut. Fig.2 shows smart probiotics control sulfur metabolism in the gut in response to environmental triggers. Fig.3 shows H2S sense and respond system to modulate intestinal H2S levels. Figs.4A-4C show preliminary results show that H2S can be consumed, stored, and produced by engineered E. coli. Fig.4A shows H2S consumption rate. Fig.4B shows GSH- 10 FH12512877.6 Attorney Docket No.: NEX-16225 H2S conversion rate. Fig.4C shows that engineered microbe sequesters H2S and accumulates intracellular GSH. GSH = glutathione, WT = wild type, P2 = pathway 2. Figs.5A-5E show characterization of GMPS and synthetic biology strategy. Fig.5A shows exploded view of the GMPS. Layers were adhered with double-sided 50 µm 3M adhesive tape. Fig.5B shows full channel brightfield image of Caco-2 cells in GMPS after ten days under flow. Multiple images were stitched together to create the tiled image. Fig.5C shows immunofluorescent staining of Caco-2 cells after ten days in GMPS. Immunostaining for ZO-1 and Hoechst. The image is a z-stack maximum intensity projection. Fig.5D shows schematic of strain development and different promoter-gene combinations to control H2S titration. Different strength promoters lac, BAD, or T7, were used to control the expression of the desulfidases (cdl or yhaM) or the putative cysteine transporter, yhaO. DecR controls the yhaOM operon; yhaO is a putative cysteine transporter, and yhaM is a cysteine desulfidase. decR was deleted from MG1655 and used as the base strain moving forward. Fig.5E shows schematic of GMPS co-culture with engineered microbes and end-point analyses. Figure created with the World Wide Web at Biorender.com. Figs.6A-6C show H2S production across the gut physiological range with engineered strains in Hungate tubes. Figs.6A-6C shows H2S production quantified in Hungate tubes over four hours, starting OD6000.4. Samples were taken while maintaining a closed system. Fig.6A shows that the three knockout strains were compared to wild type MG1655 in PBS++ (non-193 growth media) or Fig.6B shows in M9 minimal media (growth media). Fig. 6C shows engineered strains tested in PBS++ (non-growth media). The blue-shaded region represents the estimated gut physiological range (300-3,400 μM H2S). n = 3 independent experiments, for Lac-cdl; n = 4 independent experiments. Error bars represent SD, and bars represent the mean value.196 *p < 0.05, ****p < 0.0001.2-way ANOVA with post hoc Tukey analysis using a 95% confidence interval. Source data can be found in the Source Data File. Figs.7A-7C show titratable microbial H2S production in the GMPS. Fig.7A shows schematic of the experimental set-up. Cysteine was perfused through the chip, and H2S was produced by the engineered strains and collected for measurement with the methylene blue assay. Figs.7A-7B show that H2S was detected from the GMPS apical and basal effluents for two days. The effluent was collected in a tube containing zinc acetate, which effectively trapped H2S into stable ZnS. Fig.7B shows apical H2S production by the low-sulfide strain on chip by IPTG-dependent induction. Concentrations in parentheses correspond to 0, 2.5, and 250 µM IPTG induction. Fig.7C shows apical H2S production from all strains tested on 11 FH12512877.6 Attorney Docket No.: NEX-16225 the chip is shown in the top half of the graph. The bottom half of the graph shows H2S detected in the basal channel for each condition. Note the y-axes have different scales. The control chip has 5 mM cysteine, chloramphenicol, and 250 µM IPTG. n = 3 independent experiments, for Control; n = 4 independent experiments. Error bars represent SD, and bars represent the mean value. **p < 0.01, ****p < 0.0001.2-way ANOVA with post hoc Tukey analysis using a 95% confidence interval. Figure created with the World Wide Web at Biorender.com. Figs.8A-8E show characterization of microbial colonization and metabolism in GMPS. Fig.8A shows schematic of the experimental set-up. Glucose diffuses into the apical channel and is metabolized into acetate by E. coli. Cysteine was perfused through the chip, and the high-sulfide strain produced H2S. Fig.8B shows apical effluents collected from GMPS experiments were used for HPLC analysis. Metabolite levels were quantified before (hour -2) and after (hours 18 and 42) the treatment condition began, either negative control conditions or inoculation of the high-sulfide strain. Control; n = 4 independent experiments and high-sulfide strain; n = 3 independent experiments. Figs.8C-8D show representative images of the co-culture.400X live confocal images, post-processed with Gaussian smoothing. Fig.8C shows high-sulfide strain expressing RFP in GMPS after two days of co- culture. Fig.8D shows Z-stack cross-sectional image of the high-sulfide strain expressing RFP and Caco-2 cell stained nuclei in the GMPS after one day of co-culture. Fig.8E shows representative image of the co-culture.100X live image of RFP expressing E. coli MG1655 with RFP and DIC filters captured with an inverted microscope. Error bars represent SD, and bars represent the mean value. Figure created with the World Wide Web at Biorender.com. Figs.9A-9D show microbially derived H2S affects Caco-2 cells in a concentration- dependent manner. Fig.9A shows schematic of the experimental set-up. Cysteine was perfused through the chip, and the engineered strains produced H2S. Paracellular diffusion into the basal channel was quantified using Lucifer Yellow, and Papp was determined. Microbially derived or exogenous H2S was metabolized into thiosulfate by Caco-2 cells and was detected with HPLC. Fig.9B shows Papp (cm / s) was determined by collecting basal effluent before (hour -4) and during treatment conditions (hours 18 and 42). Dots indicate samples taken from the same biological replicate for identifying trends in permeability before and after treatment. n = 3 independent experiments, for Control; n = 4 independent experiments. Fig.9C (left) shows apical effluent was collected and analyzed for thiosulfate via HPLC, data shown from hour 42. Fig.9C (right) shows corresponding apical H2S production levels at hour 44. E. coli + Na2S represents the high-sulfide strain (no cysteine) 12 FH12512877.6 Attorney Docket No.: NEX-16225 with exogenous Na2S. n = 3 independent experiments. Fig.9D shows Caco-2 RNA was extracted after two days of treatment. (left) Fold change expression of GADD45a mRNA levels (reference gene GAPDH). Fold change expression was normalized to the Control. (right) Corresponding apical H2S production levels at hour 44. Error bars represent SD, and bars represent the mean value. *p<0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.1- way or 2-way ANOVA with a post hoc Tukey analysis using a 95% confidence interval. For panel b, all values were compared to the control group. Figure created with the World Wide Web at Biorender.com. Figs.10A-10B show characterization of gene knockouts on cell growth. Figs.10A- 10B show that OD600 readings were taken every 10 minutes for 16 hours. Each point is an average of 3 or 4 technical replicates. Fig.10A shows OD600 measurements of strains in M9 minimal media and Fig.10B shows in M9 minimal media with 5 mM cysteine. n = 4 independent experiments, for malY n = 3 independent experiments. Fig.11 shows that Lac-cdl titrates H2S in an IPTG-dependent manner in Hungate tubes. Strains were grown and induced at different IPTG levels in shake flasks, spun down, diluted in PBS++ to OD6000.4, and 5 mM cysteine was added. Samples were taken at hours two and four while maintaining a closed system. n = 4 independent experiments. Error bars represent SD and bars represent the mean value. **p < 0.01, ***p < 0.001, and ****p < 0.0001.2-way ANOVA with post hoc Tukey analysis using a 95% confidence interval. Fig.12 shows quantification of microbial density in the GMPS. Apical and basal effluent media from the GMPS were plated and incubated overnight. CFUs were counted the following day to get a CFU / mL value. The top half of the graph represents the apical channel, and the bottom half represents the basal channel. For control, n = 4 independent experiments, for the other experimental conditions n = 3 independent experiments. Fig.13 shows thiosulfate detection from GMPS experiments. Apical effluent was collected and analyzed for thiosulfate via HPLC. n = 3 independent experiments, for Control; n = 4 independent experiments. Fig.14 shows example of H2S standard curves in PBS++ and DMEM. Standard curves were made according to the methylene blue assay. Figs.15A-15B show that human microbiome samples were cultured anaerobically overnight in a rich media, brain heart infusion media. Cells were centrifuged and resuspended in a minimal glucose media, M9.1 mM of each sulfur substrate was added, control is M9 only. Samples were measured 3 and 20 hours after incubation. Experiments done under anaerobic conditions (n=3).2-way ANOVA used to determine significance. Mean ± sd. 13 FH12512877.6 Attorney Docket No.: NEX-16225 Fig.16 shows schematic of CTX103 in vivo (left) and the engineered metabolic pathway (right). Briefly, GSH is transported into the cell and degraded through two reactions to Cys. Cys is rapidly converted to sulfide which diffuses out of the cell. The cysteine transporter, yhaO, is also expressed to scavenge any Cys that may be exported from the cell. Figure created with the World Wide Web at Biorender.com. Fig.17 shows cells were induced overnight, pelleted, and resuspended in minimal glucose media (M9) under anaerobic conditions.1 mM GSH was added to the culture. Samples were taken at 0 and 3 hours (n=1). Fig.18 shows that CTX103, or control solution, were orally gavaged to Sprague- Dawley rats (dose: 1x1010colony forming units (CFUs), Control; n=1, 1 female. CTX102; n=2, 2 male).24 hours after gavage, the animals were sacrificed, luminal contents taken from the colon, and relative H2S levels measured with gas chromatography and normalized to sample weight. Fig.19 shows schematic of CTX102 in vivo (left) and the engineered metabolic pathway (right). Briefly, l-serine and acetyl-CoA are generated from the TCA cycle. cysE** converts these into o-acetyl-l-serine, which reacts with H2S, catalyzed by cysK, to synthesize cysteine (cys). Cys is exported from the cell through passive and active transporters or converted to GSH by ligating Cys, glycine (Gly), and glutamate (Glut) catalyzed by gshF which requires 2 ATP. Figure created with the World Wide Web at Biorender.com. Figs.20A-20C show that cells were induced overnight, pelleted, and resuspended in minimal glucose media (M9) under anaerobic conditions.1.5 mM H2S was added to cultures, as well as 2 mM serine and 20 mM glycine and glutamate. Samples were taken at 0, 3 and 20 hours (n=3). Cys / GSH measured with HPLC-FLD.1-way or 2-way ANOVA used to determine significance. Mean ± sd. Figs.21A-21B show that CTX102, or empty vector control, were orally gavaged to Sprague-Dawley rats (dose: 5x1010colony forming units (CFUs), Control; n=6, 4 male 2 female. CTX102; n=6, 4 male 2 female).24 hours after gavage, the animals were sacrificed, luminal contents from the small intestine and relative H2S levels measured with gas chromatography and normalized to sample weight. Significance determined by unpaired t test with Welch’s correction. Mean ± sd. Figs.22A-22B show that cells were induced to express the thiosulfate sensing system with increasing amounts of thiosulfate, pelleted, and resuspended in LB media under aerobic conditions. H2S was added to the media. Samples were taken at 0 and 3 hours after addition 14 FH12512877.6 Attorney Docket No.: NEX-16225 of H2S (n=3 Fig.22A, n = 1 Fig.22B).1-way used to determine significance. Mean ± sd (*p<0.05 **p < 0.01). Fig.23 shows schematic of CTX111 / CTX112 in vivo (left) and the engineered metabolic pathway (right). Briefly, H2S oxidized by the SQR enzyme, and these electrons are integrated into the electron transport chain via the quinone pool (CoQ). The sulfur atom is assimilated into glutathione persulfide and other polysulfides. Figure created with the World Wide Web at Biorender.com. Figs.24A-24B show CTX111 and CTX112 were induced for two hours, pelleted, and resuspended in LB media under anaerobic conditions.1.2 mM H2S and 20 mM nitrate and fumarate were added to cultures. Samples were taken at 0, 3 and 20 hours (n=3). Significance determined by unpaired t test with Welch’s correction. Mean ± sd (*p<0.05) Fig.25 shows that CTX112 was mixed with HD-6 at varying cell density ratios in M9 media and 1 mM H2S, 20 mM nitrate, and 20 mM fumarate were added to the cultures. Samples were taken at 0, 3 and 20 hours (n=3). Mean ± sd. Fig.26 shows schematic of CTX104 in vivo (left) and the engineered metabolic pathway (right). Briefly, sulfite is transported into the cell and reduced by cysIJ. cysG synthesizes siroheme which is integrated into the cysI subunit. Figure created with the World Wide Web at Biorender.com. Fig.27 shows that CTX104 or an empty vector control was tested in anaerobic M9 media supplemented with 1 mM sodium sulfite. Samples for H2S analysis were taken after 3 hours incubation (n=3). Mean ± sd. Fig.28 shows that cells were induced to express the thiosulfate sensing system with increasing amounts of thiosulfate, pelleted, and resuspended in LB media under aerobic conditions. H2S was added to the media. Samples were taken at 0 and 3 hours after addition of H2S (n=3).1-way used to determine significance. Mean ± sd (*p<0.05). DETAILED DESCRIPTION Strains were developed to modulate intestinal H2S levels. Modulation of H2S levels is split into two modules: consumption and production. In the consumption module, we engineered two synthetic pathways for sulfide sequestration. The first pathway sequesters H2S into glutathione. The genes cysE and cysK from Escherichia coli (E. coli) were cloned and expressed in a plasmid. cysE was mutated in two places (AA167 and AA256) to prevent feedback inhibition by L-cysteine (the product). cysE transforms serine and acetyl-CoA into o-acetyl-serine (OAS), and cysK transforms H2S and OAS into L-cysteine. We then cloned 15 FH12512877.6 Attorney Docket No.: NEX-16225 the two different pathways to synthesize glutathione from cysteine. First, we cloned the homologous enzymes gshA, which ligates cysteine and glutamate into gamma-L-glutamyl-L- cysteine, and gshB, which ligates L-glutamate and into gamma-L-glutamyl-L-cysteine to form glutathione. Second, the bifunctional gshF gene from Streptococcus thermophilus was cloned which converts L-cysteine, L-glutamate, and glycine into glutathione. In the intestine, luminal H2S is consumed by the microbe and transformed into the intermediate L-cysteine, which is then converted to glutathione as a stable sulfur sink. Storing sulfur in the form of glutathione has two advantages: i) It is a known anti-oxidant and may benefit disease; and ii) Glutathione is stable in the human gut microbiome. The second pathway sequesters H2S by oxidation by a sulfide:quinone reductase (SQR) from Wolinella succinogenes or Rhodabacter capsulatus. H2S is oxidized and the electrons are transferred to the quinone pool and electron transport chain, and the sulfur atom is assimilated into glutathione persulfide, polysulfide compounds, or elemental sulfur. For the production module, we engineered two synthetic pathways for sulfide production. In the first pathway, glutathione is transported into the cell and broken down by pepT and ggt (E. coli homologous enzymes) into L-cysteinylglycine, and further broken into L-cysteine by pepB (E. coli homologous enzyme). L-cysteine is converted to sulfide by the native desulfidase, yhaM, and is passively exported to the intestinal lumen. The native L- cysteine transporter, yhaO, is expressed to sequester environmental L-cysteine for conversion to sulfide. All genes are native to E. coli. The second pathway uses a sulfite reductase to convert sulfite to sulfide. The E. coli native cysI and cysJ subunits form the CysIJ sulfite reductase and convert sulfite to sulfide. The cysG gene is also overexpressed to synthesize siroheme required for cysIJ. Genes from both the production and consumption modules can be activated or repressed by environmental cues, such as luminal H2S, reactive oxygen species (ROS), thiosulfate, or disease biomarkers such as the interleukins (IL) and pro-inflammatory compounds. For example, inflammatory cascades in inflammatory bowel disease (IBD) result in high levels of ROS, which can trigger ROS-activated promoters driving the expression of downstream genes. Furthermore, we can modify the microbe to export l-cysteine or glutathione for their antioxidant properties in IBD. In this sense, the technology can be adapted for different applications. Building on this concept, a thiosulfate-responsive system was assembled to sense environmental thiosulfate and respond by degrading H2S. The thsS, a membrane-bound thiosulfate sensor which phosphorylates the transcription factor, thsR, which binds to 16 FH12512877.6 Attorney Docket No.: NEX-16225 the phsA342 promoter to drive gene expression from Shewanella halifaxensis. This system was adapted into E. coli and senses thiosulfate to active expression of the sulfide sequestration pathways. Our data shows thiosulfate is converted to sulfide by the native human gut microbiome and serves as a biomarker for high H2S levels. In other biological scenarios, it would be advantageous to sense low luminal thiosulfate and turn on the H2S production pathways. The environmental cue can be ROS, using a ROS-activated promoter such as the oxyR and oxyS gene-promoter from E. coli. High ROS levels are associated with a pro- inflammatory environment and can be used as a signal to drive gene expression for H2S sequestration pathways. The environmental cue can be H2S, using a luminal H2S-activated promoter, such as native promoter, IR9, from B. licheniformis. We are adapting an H2S sensor from Bacillus licheniformis, specifically by cloning the nreB / C pathway. NreB senses H2S and phosphorylates the transcription factor, NreC, which binds to a native promoter from B. licheniformis. We will leverage this system to drive the expression of the consumption or production pathway, depending on the H2S concentration. The environmental cue can be pro-inflammatory biomarkers such as interleukins (IL) or other chemokines which drive a signaling cascade and drive gene expression of H2S production or consumption pathways. For example, the Nuclear factor-κB (NF-κB) transcription factors (p65 (RelA), RelB, c-Rel, p105p50 (NF-κB1), and p100 / 52 (NF-κB2)) respond to IL-1 and tumor necrosis factor (TNF) and bind to the consensus sequence 5’- GGGRNYYCC-3’ (SEQ ID NO: 52) where R = A or G; N = A, C, G, or T; W = A or T; and Y = C or T. The NF- κB transcription factors regulate hundreds of genes. The consensus binding sequence can be used to bind activated NF-κB transcription factors to drive expression of H2S consumption or production pathways in microbes. Advantages include: The disclosed microbes provide sense-and-respond therapeutic platform. Most therapeutics are 'static', meaning they cannot respond to the surrounding environment. Our microbes can sense the intestinal environment and toggle between consumption and production of sulfur species. The gut is a heterogeneous environment (large patient-to-patient variation) which gives our microbial platform an advantage over traditional one-dimensional therapies, such as chemical sulfide donors. The disclosed microbes provide recycling of a toxic metabolite (H2S) to a therapeutic metabolite (glutathione). 17 FH12512877.6 Attorney Docket No.: NEX-16225 The disclosed microbes provide a microbial platform that can be genetically modified for different applications and disease targets. We can cycle intestinal sulfur species, enabling many therapeutic targets and applications. Microbial-based consumption / delivery of sulfur compounds is advantageous over chemical donors because of dynamic control enabled by gene expression in the microbes. This can be in response to environmental factors (ROS, thiosulfate, pro-inflammatory levels, or H2S levels). Comparatively, chemical sulfide chelators or sulfide-releasing compounds are not dynamic nor targeted to specific regions in the gut. This may be advantageous because there is large patient-to-patient variation in many diseases. There are no dynamic metabolite controllers for intestinal metabolites, specifically H2S. This platform could be modified (plug-and-play of genetic elements) to regulate levels of other intestinal metabolites. People with Inflammatory Bowel Disease (IBD) have higher stool H2S levels, and it is believed this compounds drives disease pathology. Targeting intestinal metabolites is difficult and small molecule inhibitors or microbial or host enzymes results in high off-target effects. Alternatively, our sulfide-sequestering microbes could lower systemic H2S levels, without altering host metabolism. The disclosed engineered bacteria produce H2S from a sulfur source which is generally inaccessible to the native human gut microbiome, glutathione, for sulfide production. This gives the engineered microbe exclusive access to this sulfur for H2S production in a highly controllable manner. This is advantageous in a therapeutic setting. The disclosed engineered bacteria sequester H2S into intracellular and extracellular sulfur compounds that are inaccessible to the native human gut microbiome for H2S production. This will lead to a stable and reliable reduction in intestinal sulfide for therapeutic applications. Potential uses include: Hydrogen sulfide exerts its effects in a concentration-dependent manner, and therefore can exacerbate diseases when too much or too little of the compound is present in a biological setting. The disclosed microbes provide consumption of H2S in neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), an ulcer, colorectal cancer, mental retardation, Down Syndrome, intestinal pain, H2S poisoning, an inflammatory disease, a cardiometabolic 18 FH12512877.6 Attorney Docket No.: NEX-16225 disease, Ethylmalonic encephalopathy, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus, or diabetes mellitus. High H2S levels are associated with exaggerated disease. Mental retardation in Down Syndrome (DS) may be caused by high H2S levels in the blood and brain. There is higher expression of H2S-producing enzymes in people with DS which may be considered a metabolic disorder. Our engineered microbes sequester excess H2S via the intestine. H2S passively diffuses through tissue, and systemic H2S levels could be reduced via this mechanism. For example, Synlogic’s SYNB1934 is in Phase III trials and sequesters systemic phenylalanine via the gut, effectively reducing serum phenylalanine levels for PKU disease treatment. Similar to the connection between DS and H2S, excess systemic phenylalanine induces brain damage in patients with PKU. The disclosed microbes provide production of H2S in neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, an ulcer, colorectal cancer, intestinal pain, an inflammatory disease, a cardiometabolic disease, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus, or diabetes mellitus. (Low H2S levels are associated with exaggerated disease). The disclosed microbes provide delivery of antioxidants (H2S, L-cysteine, and glutathione) to sources of intestinal inflammation / damage (IBD, ulcers, colorectal cancer). The disclosed microbes provide treatments for inflammatory bowel disease (IBD), H2S- mediated mental retardation, and / or intestinal pain relief. The disclosed microbes provide pain relief in the gut. The disclosed microbes reduce bowel movements in the gut for treating diarrhea and symptomology of various gut diseases. The disclosed microbes provide treatment for H2S poisoning (usually caused by workplace exposure). 19 FH12512877.6 Attorney Docket No.: NEX-16225 Performance advantages include: The dynamic control aspect of the microbes enables the technology to toggle between production and consumption, which may enhance its efficacy and the number of patients it is helpful for. The engineered microbes are generally regarded as safe and provide unprecedented control over intestinal metabolites. Provided herein are microorganisms, systems and methods for modulating H2S. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of consuming H2S, converting H2S to L-cysteine and optionally converting L- cysteine to glutathione, or converting H2S to persulfide and polysulfide compounds. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of producing H2S, converting glutathione to L-cysteine and H2S, and converting sulfite into sulfide. Definitions For convenience, certain terms employed in the specification, examples, and appended claims are collected here. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. The term “about” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the values measured or determined, i.e., the limitations of the measurement system. Where the terms “about” or “approximately” are used in the context of compositions containing amounts of ingredients or conditions such as temperature, these values include the stated value with a variation of 0-10% around the value (X ± 10%). The terms “including,” “includes,” “having,” “has,” “with,” or variants thereof are inclusive in a manner similar to the term “comprising.” The term “consisting” and the grammatical variations of consist encompass embodiments with only the listed elements and excluding any other elements. The phrases “consisting essentially of” or “consists essentially of” encompass embodiments containing the specified materials or steps and those including materials and steps that do not materially affect the basic and novel characteristic(s) of the embodiments. Ranges are stated in shorthand to avoid having to set out at length and describe each and every value within the range. Therefore, when ranges are stated for a value, any 20 FH12512877.6 Attorney Docket No.: NEX-16225 appropriate value within the range can be selected, and these values include the upper value and the lower value of the range. For example, a range of two to thirty represents the terminal values of two and thirty, as well as the intermediate values between two to thirty, and all intermediate ranges encompassed within two to thirty, such as two to five, two to eight, two to ten, etc. The term “genetic modification” as used herein refers to altering the genomic DNA in a microorganism. Typically, a genetic modification alters the expression and / or activity of a protein encoded by the altered gene. A genetic modification encompasses a “variant”, which is a gene or protein sequence that deviates from a reference gene or protein, as further detailed below. The term “microorganism” refers to prokaryote or eukaryote microorganisms capable of oligosaccharides production or utilization with or without modifications. The term “parental microorganism” refers to a microorganism that is manipulated to produce a genetically modified microorganism. For example, if a gene is mutated in a microorganism by one or more genetic modifications, the microorganism being modified is a parental microorganism of the microorganism carrying the one or more genetic modifications. The term “gene” includes the coding region of the gene as well as the upstream and downstream regulatory regions. The upstream regulatory region includes sequences comprising the promoter region of the gene. The downstream regulatory region includes sequences comprising the terminator region. Other sequences may be present in the upstream and downstream regulatory regions. A gene is represented herein in small caps and italicized format of the name of the gene, whereas a protein is represented in all caps and non-italicized format of the name of the protein. For example, cdt-1 (italicized) represents a gene encoding the CDT-1 protein, whereas CDT-1 (non-italicized and all caps) represents CDT-1 protein. The sequence identity of at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% to a reference sequence refers to a comparison made between two sequences, preferably using the BLAST algorithm. Algorithms for comparisons between two protein sequences that use protein structural information, such as sequence threading or 3D- 1D profiles, are also known in the field. A “variant” is a gene or protein sequence that deviates from a reference gene or protein. The terms “isoform,” “isotype,” and “analog” also refer to “variant” forms of a gene or a protein. The variant may have “conservative” changes, wherein a substituted amino acid has similar structural or chemical properties, e.g., replacement of leucine with isoleucine. A 21 FH12512877.6 Attorney Docket No.: NEX-16225 variant may have “nonconservative” changes, e.g., replacement of a glycine with a tryptophan. Analogous minor variations may also include amino acid deletions or insertions, or both. Suitable amino acid residues that may be substituted, inserted, or deleted, and which are “conservative” or “nonconservative” may be determined by those of skill in the art, including by using computer programs well known in the art. “Exogenous nucleic acid” refers to a nucleic acid, DNA, or RNA, which has been artificially introduced into a cell. Such exogenous nucleic acid may or may not be a copy of a sequence or fragments thereof which is naturally found in the cell into which it was introduced. “Endogenous nucleic acid” refers to a nucleic acid, gene, polynucleotide, DNA, RNA, mRNA, or cDNA molecule that is naturally present in a microorganism. An endogenous sequence is “native” to, i.e., indigenous to, the microorganism. The term “mutation” refers to genetic modification to a gene including modifications to the open reading frame, upstream regulatory region, and / or downstream regulatory region. A heterologous host cell for a nucleic acid sequence refers to a cell that does not naturally contain the nucleic acid sequence. A “chimeric nucleic acid” comprises a first nucleotide sequence linked to a second nucleotide sequence, wherein the second nucleotide sequence is different from the sequence which is associated with the first nucleotide sequence in cells in which the first nucleotide sequence occurs naturally. A constitutive promoter expresses an operably linked gene when RNA polymerase holoenzyme is available. Expression of a gene under the control of a constitutive promoter does not depend on the presence of an inducer. An inducible promoter expresses an operably linked gene only in the presence of an inducer. An inducer activates the transcription machinery that induces the expression of a gene operably linked to an inducible promoter. The term “preventing” is art-recognized, and when used in relation to a condition, such as a local recurrence, is well understood in the art, and includes administration of a composition which reduces the frequency of, or delays the onset of, symptoms of a medical condition in a subject relative to a subject which does not receive the composition. Thus, prevention of seizures includes, for example, reducing the number of seizures in a population of patients receiving a prophylactic treatment relative to an untreated control population, and / or delaying the appearance of detectable lesions in a treated population versus an untreated control population, e.g., by a statistically and / or clinically significant amount. 22 FH12512877.6 Attorney Docket No.: NEX-16225 The term “subject” refers to a mammal, including, but not limited to, a human or non- human mammal, such as a bovine, equine, canine, ovine, or feline. A “therapeutically effective amount” of a compound with respect to the subject method of treatment refers to an amount of the compound(s) in a preparation which, when administered as part of a desired dosage regimen (to a mammal, preferably a human) alleviates a symptom, ameliorates a condition, or slows the onset of disease conditions according to clinically acceptable standards for the disorder or condition to be treated or the cosmetic purpose, e.g., at a reasonable benefit / risk ratio applicable to any medical treatment. As used herein, the term “treating” or “treatment” includes reversing, reducing, or arresting the symptoms, clinical signs, and underlying pathology of a condition in a manner to improve or stabilize a subject's condition. As used herein, the term “administering” means providing a therapeutic agent or composition to a subject, and includes, but is not limited to, administering by a medical professional and self-administering. The means of providing a therapeutic agent are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, intraaural administration, intracerebral administration, rectal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. As used herein, the term “treatment” refers to clinical intervention designed to alter the natural course of the individual being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of progression, ameliorating or palliating the pathological state, and remission or improved prognosis of a particular disease, disorder, or condition. An individual is successfully “treated,” for example, if one or more symptoms associated with a particular disease, disorder, or condition are mitigated or eliminated. Methods for Modulating Hydrogen Sulfide Concentrations in the Human Intestine Despite the promise of microbial and H2S-based therapeutics, there remains a significant technical challenge in modifying H2S levels in the human intestinal environment due to its volatility. There are currently no metabolite controllers for H2S. Overcoming this 23 FH12512877.6 Attorney Docket No.: NEX-16225 challenge could enable a dramatic expansion in the disease target portfolio and could serve as a platform for modulating other intestinal metabolites of interest. Accordingly, there is need for methods for modifying H2S levels in the human intestinal environment. This problem is solved by developing strains to modulate intestinal H2S levels. The concept is depicted in Fig.2. In our approach, modulating H2S levels is split into two modules: consumption and production. In the consumption module (Fig.2, steps 1-3), we engineered a synthetic pathway for sulfide sequestration and intracellular storage of sulfur in the form of glutathione. In the intestine, luminal H2S is consumed and transformed into the intermediate L-cysteine, which is then converted to glutathione as a stable sulfur sink. Storing sulfur in the form of glutathione has two advantages: i) It has anti-inflammatory properties in disease; and ii) Glutathione is stable and not converted by the human gut microbiome. For the production module (Fig.2, steps 4-6), intracellular glutathione is broken down into L- cysteine which is converted to sulfide for passive export to the intestinal lumen. In Fig.2 steps 2-5, genes in both the production and consumption modules can be activated or repressed by environmental cues, such as luminal sulfide, thiosulfate, disease biomarkers, or reactive oxygen species (ROS). For example, inflammatory cascades in IBD result in high levels of ROS, which can trigger ROS-activated promoters driving expression of downstream genes. Furthermore, in steps 2a, 3a, and 4a, there is the option to export l- cysteine or glutathione for their antioxidant properties in IBD. Alternatively, overexpressing the H2S sequestering pathway may prove therapeutic for mental retardation in patients with Down Syndrome. The technology can be adapted for different applications. Building on this concept, we are developing a microbe that senses and responds to luminal H2S levels to maintain a therapeutic level (Fig.3). We are adapting an H2S sensor from Bacillus licheniformis, specifically the nreB / C pathway. The nreB / C pathway is activated in the presence of sulfide which we leverage to drive expression of the consumption or production pathway, depending on the H2S concentration. The concept of metabolic dynamic control has gained increasing attention in the last decade as a promising method to enhance microbial product synthesis. To the best of our knowledge, a dynamic microbial controller for intestinal metabolites, specifically H2S, has never been developed. Other groups have developed sulfur recycling in microbes for L-cysteine overproduction based on a H2S2sensing system and sensing of hydrogen polysulfide (HSnH), a by-product of H2S oxidation, for quorum sensing. Another technology that comes from this is the ability to accumulate excess glutathione in E. coli prior to deployment in the gut. For example, the unpredictable intestinal 24 FH12512877.6 Attorney Docket No.: NEX-16225 environment may lack adequate sulfur sources and precursors for L-cysteine and glutathione synthesis, so large intracellular glutathione pools will ensure the microbe can access a sulfur source for H2S production while traversing the intestine. We have also developed a strain that can convert extracellular sulfite into hydrogen sulfide. Sulfite has been shown to affect the gut microbiota at concentrations typically found in food. Microbial metabolism in the human gut is increasingly linked with a range of host diseases. Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H2S, and the use of model systems that do not accurately represent the human gut environment. Here, we engineered E. coli to titrate H2S across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was engineered to maintain H2S gas tension and enabled visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal and in vitro models. These findings motivated the development of microbes capable of sequestering or producing intestinal H2S from different sulfur sources found in the human intestine. First, we engineered a synthetic pathway that converts H2S to glutathione. The strain consumed H2S at a rate of 1 mM H2S / hr-OD600, approximately 10-fold higher than wild type. Next, we engineered a synthetic pathway to convert glutathione to H2S which can produce 0.3 mM H2S / hr-OD600compared to no H2S production in the wild type. These engineered microbes may be used to modify the intestinal metabolome to drive changes in human disease pathology. Engineered bacteria titrate hydrogen sulfide and induce concentration dependent effects on host in a gut microphysiological system Extensive research has linked dysbiosis in the gut microbiota with human disease. In particular, microbiome composition is implicated in intestinal diseases such as irritable bowel syndrome (IBS), colorectal cancer, and Crohn’s disease. Unfortunately, our mechanistic understanding of how specific microbes contribute to disease lags behind. One of the methods by which bacteria exert influence on host health is through their production and 25 FH12512877.6 Attorney Docket No.: NEX-16225 breakdown of small molecule metabolites that act as chemical messengers between microbes and host cells. Hydrogen sulfide (H2S), a metabolite produced by both host cells and the microbiota, is implicated in various gut diseases, but the underlying mechanisms are not understood and its role is debated. Colonic H2S is produced by sulfate-reducing bacteria (SRB) and cysteine-degrading bacteria, with the latter being more abundant in the microbiome. Several lines of evidence support a role for H2S as a toxic mediator of inflammation. Patients with inflammatory bowel disease (IBD) and ulcerative colitis (UC) present with higher SRB composition and fecal H2S levels, respectively. In vitro studies have shown H2S donors induce cell cycle arrest in immortalized intestinal epithelial Caco-2 cells and affect proliferation of the immortalized intestinal epithelial cell line, HCT116, in a concentration-dependent manner. Additionally, at high concentration, H2S inhibits colonocyte oxygen consumption and butyrate oxidation, and intra-colonic injection of the sulfide donor NaHS leads to an up-regulation of inflammation-related genes. Finally, colonization of genetically predisposed (IL10- / -) mice with the H2S producer Atopobium parvulum leads to a worsening of colitis, with the effect being reversed by treatment with bismuth, an H2S scavenger. By contrast, other evidence points to H2S as an agent of stability at the mucosal interface. In rats, H2S donors enhance gastric ulcer healing and colitis resolution. In addition, inhibition of host H2S synthesis leads to increased susceptibility to mucosal injury, and low concentrations of H2S increase metabolic activity in colonocytes. H2S’s role as a therapeutic or toxic mediator in each process is therefore contradictory, and appears to depend on concentration, the model system used, and the route of administration. Further complicating the interpretation of these studies are the technical challenges associated with controlling and measuring this reactive, volatile metabolite in the intestine. Thus, a means to reliably control H2S concentration in the gut microenvironment would help to elucidate its concentration-dependent effects in human tissues. To study microbially derived metabolites and their effects on the host, researchers have generally used two approaches: knocking out or overexpressing biosynthetic gene clusters in relevant bacteria and evaluating their impact in vivo; or introducing the metabolite in a static in vitro system (e.g. Transwell) by direct addition or the use of spent microbial media. Both approaches present challenges. While animal models can recreate the complex biology of the gut, unfortunately findings often do not translate to human health with high accuracy due to species differences in anatomy and genetics. Additionally, their use poses ethical issues. Mice colonized with a human microbiota are an advancement, but may not capture specific interactions in the human gut that have arisen from the co-evolution of the 26 FH12512877.6 Attorney Docket No.: NEX-16225 host and microbiota. For static microbial / human cell co-cultures, the lack of fluid flow leads to microbial overgrowth in co-cultures, so only short time scales can be explored. By contrast, in vitro flow systems, such as the gut-on-a-chip (GoC), are emerging as excellent models for studying host-microbe interactions. They are easier to probe than animal models, and recreate certain organ level functions like transport, digestion, and metabolism better than static Transwell and intestinal organoid cultures. Further, GoC systems are under physiological flow, which is necessary for establishing complex microbiomes and enabling the study of host-microbe interactions. Researchers have also begun to use GoC systems to test the activity of therapeutic microbes as an orthogonal preclinical model. Recently, in vivo function of a synthetic probiotic for phenylketonuria was recreated with high accuracy in a GoC model, highlighting the utility of chips in bridging the in vitro to in vivo gap. Further, chips enable direct manipulation and measurement of the gut metabolome, which led to the discovery of metabolites that activate the pathogenesis of enterohemorrhagic Escherichia coli. This study would have been challenging in mice due to the difficulty in modulating and measuring individual metabolites along the digestive tract. Previous GoC models have primarily been comprised of polydimethylsiloxane (PDMS), permeable to gas molecules. Investigating the impact of gaseous mediators like nitric oxide (NO), carbon monoxide (CO), and H2S on gut homeostasis is not feasible using PDMS without surface modifications to reduce permeability, or using atmosphere-controlled incubators. We have recently developed a cut & assembled method for manufacturing reconfigurable microphysiological systems (MPS), including gut-MPS (‘GMPS’ or ‘chip’), models out of thermoplastics to retain gas tension on the chip precisely for investigating gasotransmitters. We therefore hypothesized that our gas tension-retaining GMPS would provide the ideal opportunity to address hypotheses about H2S-host interactions that are infeasible with traditional model systems. In this work, we engineered a library of microbial strains that reliably titer H2S across the gut physiological range, and used them to investigate the concentration-dependent effects of H2S on the host epithelium in our GMPS. Tunable production was achieved via titratable expression of L-cysteine (cysteine) desulfidase, which catalyzes the conversion of cysteine to H2S. Through a combination of gene knockouts, screening of heterologous and native desulfidases, different strength promoters, and transporter engineering, we generated a library of strains capable of titrating H2S across the gut physiological range (300-3,400 μM) in Hungate tubes. Our engineered strains were inoculated and stably colonized the GMPS for at least two days, actively metabolizing glucose and titrating H2S (75 – 1,200 μM) over the 27 FH12512877.6 Attorney Docket No.: NEX-16225 duration of the chip experiment. RT-qPCR analysis of epithelial cells showed an H2S concentration-dependent effect on host expression of GADD45a, a gene involved in DNA damage and cell cycle arrest known to be upregulated in the presence of H2S. Additionally, metabolic analysis of co-culture effluent from the lumen channel showed host oxidation of microbial H2S into thiosulfate. Finally, our platform allows for live visualization of colonization with confocal fluorescence microscopy. Overall, we have validated a powerful platform combining synthetic biology and GMPSs for investigating the role of H2S in the gut, which supports fundamental discoveries in human health. Discussion Investigating the mechanistic role of microbially derived metabolites on host biology remains experimentally difficult. Specifically, the inability to accurately model human intestinal biology in 2D static cultures, coupled with the limited tools to control and measure gut metabolite levels in vivo make it difficult to accurately titrate relevant metabolites in a physiologically relevant experimental system. We posited that metabolically engineering microbes in a GMPS to produce the desired metabolite from resources available in the gut could represent a generalizable approach to address these challenges. In this proof-of-concept study, we focused on H2S owing to i) its debated role in human gut diseases, ii) the wide and uncertain range of physiologically relevant concentrations reported, and iii) its volatility, which makes it challenging to study with conventional static cultures, where exogenous sources of H2S either evaporate quickly or are slowly released through chemical donors with unpredictable breakdown kinetics. We used a synthetic biology approach to develop a small E. coli strain library that successfully titrated H2S across this wide range. Interestingly, we discovered a synergistic effect on H2S production when co-expressing the E. coli cysteine transporter (yhaO) and desulfidase (yhaM), with this strain resulting in 210% more H2S than the total production from strains expressing these genes individually. This suggests that high H2S production is limited by the cell’s capacity both for cysteine transport and catalysis. Compared to the transport of other amino acids, uptake of cysteine is poorly characterized, and dedicated transporters are not widely distributed. Because of this, it has been posited that the preferred source of sulfur for microbes in anoxic conditions like the gut is H2S, since it can freely diffuse across the cell membrane, allowing cells to avoid the energy investment in transport. As such, overexpression of the yhaO transporter in our strain may allow it to compete effectively for cysteine in a more complex microbiome, enabling its deployment in in vivo models. 28 FH12512877.6 Attorney Docket No.: NEX-16225 Once in co-culture on the chip, the strains produced H2S across the gut physiological range. The low-sulfide strain, expressing a heterologous desulfidase, controllably produced H2S across a ~200 μM range through IPTG titration. This result showcases the high degree of control over microbially-derived H2S levels in our GMPS, which was unachievable with the exogenous sulfide donor, Na2S. Compared to microbially derived H2S, dosing exogenous Na2S resulted in a larger variance in H2S effluent measurements, effect on Papp, and GADD45a mRNA expression. Na2S is not a natural sulfide source in the human gut, and HPLC analysis showed different thiosulfate profiles when compared to cysteine-derived sulfide, which is a major production pathway in the human gut. Additionally, diffusion of H2S to the epithelial cell surface may depend on gut biogeography. For example, Desulfibrio spp., major H2S producers in the human gut, colonize and metabolize gut mucus and may produce local sulfide gradients which would not be replicated by small-molecule sulfide donors. Collectively, these results highlight the advantages of using engineered microbes over chemical donors for precise modulation of the gut metabolome. There are several advantages to use of our GMPS platform. First, the system was designed with gas impermeable materials that retain gas tension better than PDMS, specifically to study volatile metabolites. The experiments reported here would have been infeasible in PDMS-based GoC systems due to H2S evaporation. Second, compared to static co-culture with organoids, the constant fluid flow in the system promotes the stable co- culture of microbes and host epithelial cells, enabling longer duration experiments without the problems of microbial overgrowth. We successfully maintained the system for 48 hours. There were no experimental factors that prevented co-cultures beyond two days (e.g. overgrowth, Caco-2 cell death), so future work could explore chronic sulfide effects on the host. Third, we engineered the system to be optically transparent, enabling real-time visualization of E. coli colonization without the need to terminate the experiment. The stable colonization of this chip is likely attributable to mucus production, as shown previously in our GMPS. Finally, compared to mouse models, our GMPS permits higher-throughput experimentation, and its use of human tissue overcomes some of the limitations arising from different species. Direct access to the lumen and apical material in the simplified system facilitates the experimental study of host-microbiota metabolic cross-talk, which is experimentally challenging in mice. One limitation in our study is the lack of a complex microbiota, which that may modulate the effects of sulfide on the host, and impact H2S production through competition for cysteine. A previous study using mice showed that introduction of a H2S-producing 29 FH12512877.6 Attorney Docket No.: NEX-16225 microbe, Atopobium parvulum, induced colitis only in the presence of an intact microbiota. Thus, it would be interesting to examine the impact of controlled sulfide production on-chip using our strains in the presence of additional gut bacteria. This could be done in our system by taking advantage of the gas impermeability to establish oxygen gradients supportive of aerobic and anaerobic bacteria, as has been done in other GoC systems. Regarding cysteine competition, as described above, the expression of a dedicated cysteine transporter may enhance the competitiveness of our strain. In addition, we could explore other pathways for H2S production. For example, E. coli can accumulate the tripeptide glutathione at very high levels intracellularly. This could be mobilized into cysteine on-chip by controlled induction of specific peptidases, then converted to H2S as described here, providing a source of microbial sulfide inaccessible to other microbes. Additionally, as gut-related disorders involve an immune component, expanding the types of human tissue used in our GMPS could allow further interrogation of important aspects of the host response. While not inclusive of the biodiversity in the human gut, we note that the immortalized Caco-2 cell line used here was chosen to minimize the biological variability present in primary cultures, as the focus was on assessing the potential of engineered bacteria to manipulate metabolite levels. Future studies will incorporate additional cell types in order to further explore the biological implications of H2S production, and identify factors underlying the robustness of our engineered bacteria. We believe the combination of engineered microbes and the GMPS is a powerful platform for addressing a range of important topics. The gas-impermeable nature of our platform could be leveraged to ask fundamental questions about the other microbiota-derived gasotransmitters, NO and CO. These gaseous mediators likely affect the stromal gut enteric nervous and immune systems. Studying these gases in animal models is more complicated than soluble metabolites due to their volatility and rapid diffusion through tissue. In our study, basal H2S was detected on the chip at concentrations similar to human serum. This lays the foundational groundwork to incorporate vascular, neuronal, or immune cells in the basal compartment to investigate how microbiota-derived gasotransmitters affect the local tissue environment. This platform is not limited to gaseous metabolites. Synthetic biology allows for plug-and-play of different genetic elements to study other metabolites, such as neurotransmitters. Gut microbes affect the brain’s neurotransmitter pool by modulating precursors in the gut that communicate via the gut-brain-axis . More broadly, translating synthetic probiotics from test tubes to the clinic will require extensive validation and additional engineering to ensure robust performance in the complex 30 FH12512877.6 Attorney Docket No.: NEX-16225 gut environment. Incorporating the GMPS into the design-build-test-learn cycle for smart probiotics could help identify factors underlying strain stability, performance, and robustness at lower cost and with more fidelity than mouse studies. Critically, GoC systems have accurately predicted the in vivo strain activity of a clinical biotherapeutic, supporting their role as an orthogonal pre-clinical model. Overall, we have validated a powerful platform combining synthetic biology and gas tension-retaining GMPSs for investigating the role of gaseous mediators in the human intestine. This platform enables precise manipulation of the gut metabolome, which we leveraged to understand the concentration-dependent effects of H2S on human gut epithelial cells. This platform will allow researchers to experimentally address host-microbe hypotheses that are infeasible with current animal and in vitro models. Microorganisms, systems and methods for Modulating H2S Heterologous genes and enzymes Heterologous expression means that a protein is experimentally put into a cell that does not normally make (i.e., express) that protein. Heterologous (meaning ‘derived from a different organism’) refers to the fact that often the transferred protein was initially cloned from or derived from a different cell type or a different species from the recipient. Typically, the protein itself is not transferred, but instead the genetic material coding for the protein (the complementary DNA or cDNA) is added to the recipient cell. Methods for transferring foreign genetic material into a recipient cell include transfection and transduction. H2S Consumption Provided herein are microorganisms, systems and methods for modulating H2S. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of consuming H2S. For example, the microorganism described herein can converts H2S to L-cysteine and optionally converts L-cysteine to glutathione. In some embodiments, the microorganism is genetically engineered to express a serine acetyltransferase, or homologs and variants thereof. CysE: Serine acetyltransferase carries out the first step in the pathway of cysteine biosynthesis, converting L-serine into O-acetyl-L-serine. An example of serine acetyltransferase is provided by the sequence of SEQ ID NO: 1, which is serine acetyltransferase from Escherichia coli. Homologues of serine acetyltransferase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of 31 FH12512877.6 Attorney Docket No.: NEX-16225 serine acetyltransferase in the instant invention are represented by UniProt entries: P0A9D4, Q06750, P95231, A0A120HUS7, P29847, Q8CTU2, P71405, P77985, P67765, Q6GBV9, P57162, P67764, P0A9D7, Q89B11, Q5HIE6, Q6GJE0, P67766, Q5HRM4, P32003, P43886, Q65PC9, Q9ZK14, Q56002, P74089, A8F961, P0A9D5, and P0A9D6. An example of serine acetyltransferase is provided by the amino acid sequence of SEQ ID NO: 1 or 3, which is serine acetyltransferase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 2 or 4. The UniProt entries listed herein are incorporated by reference in their entireties. cysE (E. coli wild type) 1 MSCEELEIVW NNIKAEARTL ADCEPMLASF YHATLLKHEN LGSALSYMLA 51 NKLSSPIMPA IAIREVVEEA YAADPEMIAS AACDIQAVRT RDPAVDKYST 101 PLLYLKGFHA LQAYRIGHWL WNQGRRALAI FLQNQVSVTF QVDIHPAAKI 151 GRGIMLDHAT GIVVGETAVI ENDVSILQSV TLGGTGKSGG DRHPKIREGV 201 MIGAGAKILG NIEVGRGAKI GAGSVVLQPV PPHTTAAGVP ARIVGKPDSD 251 KPSMDMDQHF NGINHTFEYG DGI (SEQ ID NO: 1) cysE (E. coli wild type) 1 atgTCGTGTG AAGAACTGGA AATTGTCTGG AACAATATTA AAGCCGAAGC 51 CAGAACGCTG GCGGACTGTG AGCCAATGCT GGCCAGTTTT TACCACGCGA 101 CGCTACTCAA GCACGAAAAC CTTGGCAGTG CACTGAGCTA CATGCTGGCG 151 AACAAGCTGT CATCGCCAAT TATGCCTGCT ATTGCTATCC GTGAAGTGGT 201 GGAAGAAGCC TACGCCGCTG ACCCGGAAAT GATCGCCTCT GCGGCCTGTG 251 ATATTCAGGC GGTGCGTACC CGCGACCCGG CAGTCGATAA ATACTCAACC 301 CCGTTGTTAT ACCTGAAGGG TTTTCATGCC TTGCAGGCCT ATCGCATCGG 351 TCACTGGTTG TGGAATCAGG GGCGTCGCGC ACTGGCAATC TTTCTGCAAA 401 ACCAGGTTTC TGTGACGTTC CAGGTCGATA TTCACCCGGC AGCAAAAATT 451 GGTCGCGGTA TCATGCTTGA CCACGCGACA GGCATCGTCG TTGGTGAAAC 501 GGCGGTGATT GAAAACGACG TATCGATTCT GCAATCTGTG ACGCTTGGCG 551 GTACGGGTAA ATCTGGTGGT GACCGTCACC CGAAAATTCG TGAAGGTGTG 601 ATGATTGGCG CGGGCGCGAA AATCCTCGGC AATATTGAAG TTGGGCGCGG 651 CGCGAAGATT GGCGCAGGTT CCGTGGTGCT GCAACCGGTG CCGCCGCATA 701 CCACCGCCGC TGGCGTTCCG GCTCGTATTG TCGGTAAACC AGACAGCGAT 751 AAGCCATCAA TGGATATGGA CCAGCATTTC AACGGTATTA ACCATACATT 801 TGAGTATGGG GATGGGATCt aa (SEQ ID NO: 2) 32 FH12512877.6 Attorney Docket No.: NEX-16225 cysE (E coli origin, mutated at positions 167 and / or 256) 1 MSCEELEIVW NNIKAEARTL ADCEPMLASF YHATLLKHEN LGSALSYMLA 51 NKLSSPIMPA IAIREVVEEA YAADPEMIAS AACDIQAVRT RDPAVDKYST 101 PLLYLKGFHA LQAYRIGHWL WNQGRRALAI FLQNQVSVTF QVDIHPAAKI 151 GRGIMLDHAT GIVVGEAAVI ENDVSILQSV TLGGTGKSGG DRHPKIREGV 201 MIGAGAKILG NIEVGRGAKI GAGSVVLQPV PPHTTAAGVP ARIVGKPDSD 251 KPSMDM (SEQ ID NO: 3) cysE (E coli origin, mutated at positions 167 and / or 256) 1 atgTCGTGTG AAGAACTGGA AATTGTCTGG AACAATATTA AAGCCGAAGC 51 CAGAACGCTG GCGGACTGTG AGCCAATGCT GGCCAGTTTT TACCACGCGA 101 CGCTACTCAA GCACGAAAAC CTTGGCAGTG CACTGAGCTA CATGCTGGCG 151 AACAAGCTGT CATCGCCAAT TATGCCTGCT ATTGCTATCC GTGAAGTGGT 201 GGAAGAAGCC TACGCCGCTG ACCCGGAAAT GATCGCCTCT GCGGCCTGTG 251 ATATTCAGGC GGTGCGTACC CGCGACCCGG CAGTCGATAA ATACTCAACC 301 CCGTTGTTAT ACCTGAAGGG TTTTCATGCC TTGCAGGCCT ATCGCATCGG 351 TCACTGGTTG TGGAATCAGG GGCGTCGCGC ACTGGCAATC TTTCTGCAAA 401 ACCAGGTTTC TGTGACGTTC CAGGTCGATA TTCACCCGGC AGCAAAAATT 451 GGTCGCGGTA TCATGCTTGA CCACGCGACA GGCATCGTCG TTGGTGAAgC 501 GGCGGTGATT GAAAACGACG TATCGATTCT GCAATCTGTG ACGCTTGGCG 551 GTACGGGTAA ATCTGGTGGT GACCGTCACC CGAAAATTCG TGAAGGTGTG 601 ATGATTGGCG CGGGCGCGAA AATCCTCGGC AATATTGAAG TTGGGCGCGG 651 CGCGAAGATT GGCGCAGGTT CCGTGGTGCT GCAACCGGTG CCGCCGCATA 701 CCACCGCCGC TGGCGTTCCG GCTCGTATTG TCGGTAAACC AGACAGCGAT 751 AAGCCATCAA TGGATATG (SEQ ID NO: 4) In some embodiments, the microorganism is genetically engineered to express a cysteine synthase A, or homologs and variants thereof. CysK: Cysteine synthase A carries out the second step in the pathway of cysteine biosynthesis, converting O-acetyl-serine into L-cysteine. An example of cysteine synthase A is provided by the sequence of SEQ ID NO: 5, which is cysteine synthase A from Escherichia coli. Homologues of serine acetyltransferase from microorganisms other than Escherichia coli can be used in the microorganisms and 33 FH12512877.6 Attorney Docket No.: NEX-16225 methods described herein. Non-limiting examples of the homologs of serine acetyltransferase in the instant invention are represented by UniProt entries: P0ABK5, P37887, P0A1E3, and P9WP55. An example of cysteine synthase A is provided by the amino acid sequence of SEQ ID NO: 5, which is cysteine synthase A from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 6. The UniProt entries listed herein are incorporated by reference in their entireties. cysK (E. coli wild type) 1 MSKIFEDNSL TIGHTPLVRL NRIGNGRILA KVESRNPSFS VKCRIGANMI 51 WDAEKRGVLK PGVELVEPTS GNTGIALAYV AAARGYKLTL TMPETMSIER 101 RKLLKALGAN LVLTEGAKGM KGAIQKAEEI VASNPEKYLL LQQFSNPANP 151 EIHEKTTGPE IWEDTDGQVD VFIAGVGTGG TLTGVSRYIK GTKGKTDLIS 201 VAVEPTDSPV IAQALAGEEI KPGPHKIQGI GAGFIPANLD LKLVDKVIGI 251 TNEEAISTAR RLMEEEGILA GISSGAAVAA ALKLQEDESF TNKNIVVILP 301 SSGERYLSTA LFADLFTEKE LQQ (SEQ ID NO: 5) cysK (E. coli wild type) 1 atgAGTAAGA TTTTTGAAGA TAACTCGCTG ACTATCGGTC ACACGCCGCT 51 GGTTCGCCTG AATCGCATCG GTAACGGACG CATTCTGGCG AAGGTGGAAT 101 CTCGTAACCC CAGCTTCAGC GTTAAGTGCC GTATCGGTGC CAACATGATT 151 TGGGATGCCG AAAAGCGCGG CGTGCTGAAA CCAGGCGTTG AACTGGTTGA 201 ACCGACCAGC GGTAATACCG GGATTGCACT GGCCTATGTA GCTGCCGCTC 251 GCGGTTACAA ACTCACCCTG ACCATGCCAG AAACCATGAG TATTGAACGC 301 CGCAAGCTGC TGAAAGCGTT AGGTGCAAAC CTGGTGCTGA CGGAAGGTGC 351 TAAAGGCATG AAAGGCGCAA TCCAAAAAGC AGAAGAAATTGTCGCCAGCA 401 ATCCAGAGAA ATACCTGCTG CTGCAACAAT TCAGCAATCC GGCAAACCCT 451 GAAATTCACG AAAAGACCAC CGGTCCGGAG ATATGGGAAG ATACCGACGG 501 TCAGGTTGAT GTATTTATTG CTGGCGTTGG GACTGGCGGT ACGCTGACTG 551 GCGTCAGCCG CTACATTAAA GGCACCAAAG GCAAGACCGA TCTTATCTCT 601 GTCGCCGTTG AGCCAACCGA TTCTCCAGTT ATCGCCCAGG CGCTGGCAGG 651 TGAAGAGATT AAACCTGGCC CGCATAAAAT TCAGGGTATT GGCGCTGGTT 701 TTATCCCGGC TAACCTCGAT CTCAAGCTGG TCGATAAAGT CATTGGCATC 751 ACCAATGAAG AAGCGATTTC TACCGCGCGT CGTCTGATGG AAGAAGAAGG 34 FH12512877.6 Attorney Docket No.: NEX-16225 801 TATTCTTGCA GGTATCTCTT CTGGAGCAGC TGTTGCCGCG GCGTTGAAAC 851 TACAAGAAGA TGAAAGCTTT ACCAACAAGA ATATTGTGGT TATTCTACCA 901 TCATCGGGTG AGCGTTATTT AAGCACCGCA TTGTTTGCCG ATCTCTTCAC 951 TGAGAAAGAA TTGCAACAGt aa (SEQ ID NO: 6) In some embodiments, the microorganism is genetically engineered to express a glutathione biosynthesis bifunctional protein, or homologs and variants thereof. GshF (GshAB)is a bifunctional enzyme that acts as both a glutamate-cysteine ligase and a glutathione synthase. An example of a glutathione biosynthesis bifunctional protein (glutamate-cysteine ligase and a glutathione synthase) is provided by the sequence of SEQ ID NO: 7 or 9, which is a glutathione biosynthesis bifunctional protein from Streptococcus thermophilus. Homologues of glutathione biosynthesis bifunctional protein from microorganisms other than Streptococcus thermophilus can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of serine glutathione biosynthesis bifunctional protein in the instant invention are represented by UniProt entries: Q5M3J8, Q8DXM9, Q6ANW2, Q9CM00, Q8E399, Q5M3J8, Q65RX0, A0AMA3, Q5LYY5, Q8XK30, Q8Y3R3, Q926X7, Q71VZ1, Q82ZG8, Q8DW15, Q88UW5, A0A0A7RQH3, R9SL56, A0A0D0Y7W0, A0A0U3CHT1, D3E133, A0A140D6V9, A0A7X2T160, A0A427RZV8, A0A8B3TED9, A0A3S4XIR0, A0A1V4B0F6, A0A377IBZ0, A0A377JF93, A0A0F5RHX7, A0A378MUJ6, A0A6F9Y420, A0A6F9XJU2, D4N891, D4N892, A0A6F9XU67, A0A011N9S0, A0A075SLV1, A0A089JM53, A0A091BVG1, A0A0A0DKL9, A0A0B5QCF6, A0A0B7GNS1, A0A0D7KJX1, A0A0K9L2K6, A0A0M3G5L6, A0A0R2KQK8, A0A0Z8K7B2, A0A0Z8UDJ8, A0A116K5F8, A0A139NPH3, A0A143YHS2, A0A143YNG9, A0A143Z2A7, A0A168EVJ5, A0A1A7NRT3, A0A1A7Q2F3, A0A1B9AZ48, A0A1E9W096, A0A1F0BBP7, A0A1F1KYH0, A0A1F2HQH3, A0A1G6B488, and A0A1G6V183. An example of a glutathione biosynthesis bifunctional protein is provided by the amino acid sequence of SEQ ID NO: 7 or 9, which is a glutathione biosynthesis bifunctional protein from Streptococcus thermophilus and encoded by the nucleic acid sequence of SEQ ID NO: 8 or 10. The UniProt entries listed herein are incorporated by reference in their entireties. 35 FH12512877.6 Attorney Docket No.: NEX-16225 gshF (S. thermophilus, codon harmonized for E. coli) 1 MNLRHIIKQN HLELLFQQGS FGLEKESQRV RHDGSVVTSA HPKAFGNRSF 51 HPYIQTDFAE SQLELITPPN KKLEDTFRWL QTIHEVVWRT LPEDEFIFPL 101 SMPAGLPPEK DIKVAQLDNS VDVAYREHLV KSYGAYKQMV SGIHYNFQLD 151 PALIEALFKA QSDCRSAVEF QNSLYLKMAK NFLRYQWILL YLLSATPTVD 201 ANYFREGTAL KPNQYVRSLR SSQYGYVNAP EIVVSFDSIP QYVETLEHWV 251 NSGKLIAEKE FYSNVRLRGA KKAREFLHTG IQYLEFRLFD LNPFEPYGMS 301 LHDAQFIHYF ILLMIWLDET ADQAGVELGK ARLLEVAFED PRQETVYRDE 351 GERILNALIT MLKDLGTDEN AVKSAQEKLS QFAYPERTLC ARLVAAIEQA 401 GGYQKLGAEL AQRNKAQAFE RFYALTAFDN MELSTQALMF DAIQKGLQME 451 ILDENDQFLR LQFGEHFEYV KNGNMTSRDS YISPLIMENK VVTKKVLDKA 501 GFNVPKSLEF TTLEQAVASY SLFEGRAVVI KPKSTNYGLG ITIFQQGVHD 551 RDDFAKAVEI AFREDKEVMV EDYLSGTEYR FFVLGDETLA VLLRVPANVV 601 GDGVRTVAEL VAAKNDHPLR GDGSRTPLKK ITLGEIERLQ LKEQGLTVDS 651 VPAEGLLVQL RANSNISTGG DSIDMTDEMH PSYKALAVDI TKAMGAAVCG 701 VDLIIPDLNK PAENRLSSWG VIEANFNPMM MMHIFPYQGK SRRLTQNVIK 751 MLFPELLNA (SEQ ID NO: 7) gshF (S. thermophilus, codon harmonized for E. coli) 1 atgaacctgc ggcatattat taaacagaac catttagaac tgctgttcca 51 gcaaggatcg ttcggattag aaaaagagag ccaacgtgta cgccacgacg 101 gctcggtggt gactagcgcc cacccgaagg cgttcggcaa tcgttcgttt 151 catccgtata tacagacgga tttcgccgag agccaattag aactgattac 201 tccgccgaac aagaaattag aagatacgtt tcgctggtta cagactatcc 251 atgaagtggt ttggcggacc ctgccggaag acgaattcat ctttccctta 301 agcatgcctg cgggcctgcc gccggaaaaa gacattaaag tagcccagtt 351 agataactcg gtcgatgtgg cataccgtga acatctggtg aaatcgtacg 401 gcgcctacaa gcagatggtt agcgggattc attataactt tcaattagat 451 cccgcgctga ttgaggccct gttcaaggca caaagcgatt gccggtcggc 501 ggtggaattt caaaattcgc tgtatttaaa aatggcaaaa aacttcttac 551 gttatcagtg gattttactg tatctgctga gcgctactcc gacggtggac 601 gccaactact tccgagaggg gactgcgtta aaaccgaacc agtatgtgcg 651 tagcttacgc agctcgcagt acggatatgt aaacgcgcct gaaatcgtgg 701 tgtcgttcga cagcattccc cagtatgtgg aaaccttaga gcactgggtg 36 FH12512877.6 Attorney Docket No.: NEX-16225 751 aactcgggca aactgattgc ggaaaaagaa ttttatagca acgttcgcct 801 gcgtggagcg aaaaaagccc gtgaatttct gcatacggga atccagtatt 851 tagaattccg cttattcgat ctgaacccgt tcgaaccgta cggcatgagc 901 ctgcatgatg cgcagtttat ccactatttt atcttactga tgatttggtt 951 agatgaaacg gcggatcagg ccggcgttga actggggaaa gcgcgcctgt 1001 tagaagtagc gtttgaagac ccgcgccaag aaaccgtcta tcgtgacgaa 1051 ggcgaacgga ttctgaacgc tctgattacc atgctgaaag accttggcac 1101 tgatgaaaac gcggtgaaaa gcgcacaaga aaaattaagc caatttgctt 1151 atccggaacg gacgttatgc gcccggctgg tcgccgccat agaacaggcc 1201 ggcggctatc agaaattagg agcggaactg gcgcaacgca acaaagcgca 1251 agctttcgaa cgcttttacg ccttaaccgc tttcgataac atggaactgt 1301 cgacgcaagc tctgatgttt gatgcgattc agaaaggact gcagatggaa 1351 attttagatg aaaatgatca atttttacgc ttacagttcg gcgagcattt 1401 cgaatacgtg aaaaatggca atatgactag ccgtgacagc tacatttcgc 1451 cgttaattat ggaaaacaaa gtggtgacta aaaaagttct ggataaagcc 1501 gggttcaatg ttccgaaatc gttagaattc actaccttag aacaggcggt 1551 ggcatcgtac agcttatttg aaggacgtgc tgtggtgatt aaaccgaaaa 1601 gcaccaacta cggcctgggc atcaccattt ttcagcaagg cgtgcatgat 1651 cgtgacgatt tcgccaaagc cgtcgaaatc gcgttccgcg aagataaaga 1701 agtgatggtg gaagattatc tgagcggcac ggaataccgg tttttcgtgc 1751 tgggcgatga aaccttagcg gttctgttac gtgtgccggc gaacgtagtg 1801 ggcgacggcg ttcgtacggt ggcggaatta gtcgcggcga aaaatgatca 1851 tccgctgcgc ggcgacggca gccgcactcc gttaaaaaaa atcacgctgg 1901 gcgagattga acggctgcaa ttaaaagagc agggcctgac cgtagacagc 1951 gtgccggccg aaggattatt agttcagtta cgggcaaatt cgaacatcag 2001 caccggcggc gattcgatcg acatgacgga tgaaatgcat ccgagctata 2051 aagcgttagc cgttgacatt accaaagcca tgggagcggc ggtctgcggc 2101 gtggatttaa ttattccgga tctgaacaag ccggcggaaa atcgtctgtc 2151 gtcgtggggg gtcatcgaag ctaacttcaa cccgatgatg atgatgcaca 2201 ttttccccta tcaggggaaa agccgacgcc tgacgcaaaa cgtgattaag 2251 atgttatttc cggaactgct gaacgcatag (SEQ ID NO: 8) gshF (S. thermophilus) 1 MTLNQLLQKL EATSPILQAN FGIERESLRV DRQGQLVHTP HPSCLGARSF 37 FH12512877.6 Attorney Docket No.: NEX-16225 51 HPYIQTDFCE FQMELITPVA KSTTEARRFL GAITDVAGRS IATDEVLWPL 101 SMPPRLKAEE IQVAQLENDF ERHYRNYLAE KYGTKLQAIS GIHYNMELGK 151 DLVEALFQES GQTDMIAFKN ALYLKLAQNY LRYRWVITYL FGASPIAEQG 201 FFDQEVPEPV RSFRNSDHGY VNKEEIQVSF VSLEDYVSAI ETYIEQGDLN 251 AEKEFYSAVR FRGQKVNRSF LDKGITYLEF RNFDLNPFER IGISQTTMDT 301 VHLLILAFLW LDSPENVDQA LAQGHALNEK IALSHPLEPL PSEAKTQDIV 351 TALDQLVQHF GLGDYHQDLV KQVKAAFADP NQTLSAQLLP YIKDKSLAEF 401 ALNKALAYHD YDWTAHYALK GYEEMELSTQ MLLFDAIQKG IHFEILDEQD 451 QFLKLWHQDH VEYVKNGNMT SKDNYVVPLA MANKTVTKKI LADAGFPVPS 501 GDEFTSLEEG LAYYPLIKDK QIVVKPKSTN FGLGISIFQE PASLDNYQKA 551 LEIAFAEDTS VLVEEFIPGT EYRFFILDGR CEAVLLRVAA NVIGDGKHTI 601 RELVAQKNAN PLRGRDHRSP LEIIELGDIE QLMLAQQGYT PDDILPEGKK 651 VNLRRNSNIS TGGDSIDITE TMDSSYQELA AAMATSMGAW ACGVDLIIPD 701 ETQIATKENP HCTCIELNFN PSMYMHTYCA EGPGQAITTK ILDKLFPEIV 751 AGQT (SEQ ID NO: 9) gshF (S. thermophilus) 1 ATGACATTAA ACCAACTTCT TCAAAAACTG GAAGCTACCA GCCCTATTCT 51 CCAAGCTAAT TTTGGAATCG AGCGCGAGAG TCTACGTGTC GATAGGCAAG 101 GACAACTGGT GCATACACCT CACCCATCCT GTCTAGGAGC TCGTAGTTTC 151 CACCCCTATA TTCAGACTGA TTTTTGCGAG TTTCAGATGG AACTCATCAC 201 ACCAGTTGCC AAATCTACTA CTGAGGCTCG CCGATTTCTG GGAGCTATTA 251 CTGATGTAGC TGGCCGCTCT ATTGCTACAG ACGAGGTTCT CTGGCCTTTA 301 TCCATGCCAC CTCGTCTAAA GGCAGAGGAG ATTCAAGTTG CTCAACTGGA 351 AAATGACTTC GAACGCCATT ATCGTAACTA TTTGGCTGAA AAATACGGAA 401 CTAAACTACA AGCTATCTCA GGTATCCACT ATAATATGGA ACTGGGTAAA 451 GATTTAGTTG AGGCCTTGTT CCAAGAAAGT GGTCAGACCG ATATGATTGC 501 CTTCAAAAAC GCCCTCTATC TTAAGCTGGC TCAGAACTAC TTGCGCTACC 551 GTTGGGTGAT TACCTATCTC TTTGGGGCCT CACCCATCGC CGAACAAGGT 601 TTCTTTGACC AGGAAGTTCC AGAACCTGTG CGTTCCTTCC GTAACAGTGA 651 CCACGGCTAT GTCAATAAGG AAGAGATTCA AGTATCCTTT GTAAGTCTAG 701 AAGATTATGT CTCAGCCATT GAAACCTATA TCGAACAAGG AGATTTGAAT 751 GCAGAGAAAG AATTTTACTC AGCTGTTCGT TTCCGTGGAC AAAAGGTTAA 801 TCGTTCCTTC CTTGACAAAG GAATCACCTA CCTAGAGTTC CGTAATTTCG 851 ACCTTAACCC TTTTGAGCGT ATCGGTATTA GTCAGACTAC TATGGACACT 38 FH12512877.6 Attorney Docket No.: NEX-16225 901 GTGCACTTAC TCATTTTAGC CTTCCTTTGG CTTGATAGCC CTGAAAATGT 951 CGACCAAGCT CTTGCACAAG GCCACGCGTT AAATGAGAAA ATTGCCCTCT 1001 CTCATCCTCT AGAACCTCTA CCTTCGGAGG CTAAAACTCA GGACATTGTA 1051 ACTGCCCTAG ACCAACTGGT GCAACACTTT GGACTTGGTG ACTATCATCA 1101 AGATCTGGTT AAGCAAGTTA AGGCAGCCTT TGCGGATCCA AATCAAACGC 1151 TCTCTGCCCA GCTCTTACCC TATATCAAAG ACAAATCTCT AGCCGAATTT 1201 GCTTTAAACA AGGCTCTTGC CTATCATGAT TACGACTGGA CTGCCCACTA 1251 TGCTCTCAAG GGCTATGAAG AGATGGAACT CTCCACCCAG ATGTTGCTCT 1301 TTGATGCCAT CCAAAAGGGG ATTCACTTTG AAATATTGGA TGAGCAAGAT 1351 CAATTCCTAA AACTTTGGCA CCAAGACCAT GTTGAATACG TCAAAAACGG 1401 TAACATGACC TCAAAAGACA ACTACGTGGT TCCCCTTGCT ATGGCTAATA 1451 AGACCGTAAC CAAGAAGATT CTAGCAGATG CTGGCTTTCC AGTTCCTTCA 1501 GGAGACGAAT TTACCAGTCT TGAGGAAGGA CTTGCCTACT ACCCTCTTAT 1551 CAAGGATAAG CAAATTGTTG TCAAACCCAA GTCAACTAAC TTTGGTCTGG 1601 GAATTTCCAT TTTCCAAGAA CCTGCCAGTC TTGACAACTA TCAAAAAGCC 1651 CTTGAAATTG CTTTCGCAGA AGATACCTCT GTCCTTGTTG AAGAATTTAT 1701 TCCAGGAACC GAATACCGTT TCTTCATCTT GGATGGGCGT TGTGAGGCTG 1751 TTCTTCTGCG TGTCGCTGCC AATGTTATTG GTGATGGCAA ACACACCATT 1801 CGTGAACTAG TCGCTCAGAA AAATGCTAAT CCATTGCGTG GCCGTGATCA 1851 CCGGTCACCT CTGGAAATCA TTGAGCTAGG AGACATCGAA CAACTAATGT 1901 TAGCTCAACA GGGTTACACA CCTGATGATA TTCTCCCAGAAGGAAAAAAG 1951 GTCAATCTGC GTCGTAATTC CAACATCTCT ACAGGTGGTG ACTCTATTGA 2001 TATCACTGAG ACCATGGATT CCTCTTACCA AGAATTAGCC GCAGCCATGG 2051 CAACTAGCAT GGGCGCCTGG GCTTGCGGGG TTGATCTGAT AATTCCAGAT 2101 GAAACTCAAA TTGCCACCAA GGAAAATCCT CATTGCACCT GCATTGAGCT 2151 CAACTTTAAC CCTTCGATGT ATATGCACAC CTACTGTGCT GAGGGTCCTG 2201 GCCAAGCTAT CACTACTAAA ATCCTAGATA AACTTTTTCC AGAAATAGTG 2251 GCTGGTCAAA CTTAA (SEQ ID NO: 10) In some embodiments, the microorganism is genetically engineered to express the glutamate-cysteine ligase and a glutathione synthase, or homologs and variants thereof. GshA and GshB is a glutamate-cysteine ligase and a glutathione synthetase, respectively. 39 FH12512877.6 Attorney Docket No.: NEX-16225 An example of a glutamate-cysteine ligase or a glutathione synthase is provided by the sequence of SEQ ID NO: 11 or 13, respectively, which is a glutamate-cysteine ligase or a glutathione synthase from E. Coli. Homologues of glutamate-cysteine ligase or a glutathione synthase from microorganisms other than E. Coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of a glutamate-cysteine ligase in the instant invention are represented by UniProt entries: P9WPK7, Q54PC2, P9WPK6, P0A6W9, A0R5N1, Q8D2V5, A0A240ERG2, A0A480APB4, A0A379VLT6, A0A0F7KSP3, A0A1E3H7E4, A0A4P1KG84, A0A369QAZ4, Q926D5, A0A368A3B0, F7X981, P61379, Q5V3Q5, B5RDE8, Q7N7A4, Q7W3F2, A9HYE0, O68838, Q2NVK9, Q3IEB7, Q66E64, Q87LS2, P0A6X0, and B4EUV9. Non-limiting examples of the homologs of a glutathione synthase in the instant invention are represented by UniProt entries: P04425, Q8D335, Q8DKF1, Q54E83, Q7U3W8, Q9ABS9, Q89WL0, Q7NF44, Q87LK1, P59495, Q9KUP7, Q83Q91, Q9PC29, P57612, P58580, Q7MHK1, Q7TUG9, Q82V16, Q8PHZ5, Q9I697, Q9JYJ3, Q7W910, Q8FXW6, Q8P6P1, Q9JTJ6, P58579, Q87D42, Q8DCA9, Q7NQ65, Q7TVB0, and Q87VA4. An example of a glutamate-cysteine ligase is provided by the amino acid sequence of SEQ ID NO: 11, which is a glutamate-cysteine ligase from E. coli and encoded by the nucleic acid sequence of SEQ ID NO: 12. An example of a glutathione synthase is provided by the amino acid sequence of SEQ ID NO: 13, which is a glutathione synthase from E. coli and encoded by the nucleic acid sequence of SEQ ID NO: 14. The UniProt entries listed herein are incorporated by reference in their entireties. gshA (E. coli wild type) 1 LIPDVSQALA WLEKHPQALK GIQRGLERET LRVNADGTLA TTGHPEALGS 51 ALTHKWITTD FAEALLEFIT PVDGDIEHML TFMRDLHRYT ARNMGDERMW 101 PLSMPCYIAE GQDIELAQYG TSNTGRFKTL YREGLKNRYG ALMQTISGVH 151 YNFSLPMAFW QAKCGDISGA DAKEKISAGY FRVIRNYYRF GWVIPYLFGA 201 SPAICSSFLQ GKPTSLPFEK TECGMYYLPY ATSLRLSDLG YTNKSQSNLG 251 ITFNDLYEYV AGLKQAIKTP SEEYAKIGIE KDGKRLQINS NVLQIENELY 301 APIRPKRVTR SGESPSDALL RGGIEYIEVR SLDINPFSPI GVDEQQVRFL 351 DLFMVWCALA DAPEMSSSEL ACTRVNWNRV ILEGRKPGLT LGIGCETAQF 401 PLPQVGKDLF RDLKRVAQTL DSINGGEAYQ KVCDELVACF DNPDLTFSAR 451 ILRSMIDTGI GGTGKAFAEA YRNLLREEPL EILREEDFVA EREVSERRQQ 501 EMEAADTEPF AVWLEKHA (SEQ ID NO: 11) 40 FH12512877.6 Attorney Docket No.: NEX-16225 gshA (E. coli wild type) 1 ttgATCCCGG ACGTATCACA GGCGCTGGCC TGGCTGGAAA AACATCCTCA 51 GGCGTTAAAG GGGATACAGC GTGGGCTGGA GCGCGAAACT TTGCGTGTTA 101 ATGCTGATGG CACACTGGCA ACAACAGGTC ATCCTGAAGC ATTAGGTTCC 151 GCACTGACGC ACAAATGGAT TACTACCGAT TTTGCGGAAG CATTGCTGGA 201 ATTCATTACA CCAGTGGATG GTGATATTGA ACATATGCTG ACCTTTATGC 251 GCGATCTGCA TCGTTATACG GCGCGCAATA TGGGCGATGA GCGGATGTGG 301 CCGTTAAGTA TGCCATGCTA CATCGCAGAA GGTCAGGACA TCGAACTGGC 351 ACAGTACGGC ACTTCTAACA CCGGACGCTT TAAAACGCTG TATCGTGAAG 401 GGCTGAAAAA TCGCTACGGC GCGCTGATGC AAACCATTTC CGGCGTGCAC 451 TACAATTTCT CTTTGCCAAT GGCATTCTGG CAAGCGAAGT GCGGTGATAT 501 CTCGGGCGCT GATGCCAAAG AGAAAATTTC TGCGGGCTAT TTCCGCGTTA 551 TCCGCAATTA CTATCGTTTC GGTTGGGTCA TTCCTTATCT GTTTGGTGCA 601 TCTCCGGCGA TTTGTTCTTC TTTCCTGCAA GGAAAACCAA CGTCGCTGCC 651 GTTTGAGAAA ACCGAGTGCG GTATGTATTA CCTGCCGTAT GCGACCTCTC 701 TTCGTTTGAG CGATCTCGGC TATACCAATA AATCGCAAAG CAATCTTGGT 751 ATTACCTTCA ACGATCTTTA CGAGTACGTA GCGGGCCTTA AACAGGCAAT 801 CAAAACGCCA TCGGAAGAGT ACGCGAAGAT TGGTATTGAGAAAGACGGTA 851 AGAGGCTGCA AATCAACAGC AACGTGTTGC AGATTGAAAA CGAACTGTAC 901 GCGCCGATTC GTCCAAAACG CGTTACCCGC AGCGGCGAGT CGCCTTCTGA 951 TGCGCTGTTA CGTGGCGGCA TTGAATATAT TGAAGTGCGT TCGCTGGACA 1001 TCAACCCGTT CTCGCCGATT GGTGTAGATG AACAGCAGGT GCGATTCCTC 1051 GACCTGTTTA TGGTCTGGTG TGCGCTGGCT GATGCACCGG AAATGAGCAG 1101 TAGCGAACTT GCCTGTACAC GCGTTAACTG GAACCGGGTG ATCCTCGAAG 1151 GTCGCAAACC GGGTCTGACG CTGGGTATCG GCTGCGAAAC CGCACAGTTC 1201 CCGTTACCGC AGGTGGGTAA AGATCTGTTC CGCGATCTGA AACGCGTCGC 1251 GCAAACGCTG GATAGTATTA ACGGCGGCGA AGCGTATCAGAAAGTGTGTG 1301 ATGAACTGGT TGCCTGCTTC GATAATCCCG ATCTGACTTT CTCTGCCCGT 1351 ATCTTAAGGT CTATGATTGA TACTGGTATT GGCGGAACAG GCAAAGCATT 1401 TGCAGAAGCC TACCGTAATC TGCTGCGTGA AGAGCCGCTG GAAATTCTGC 1451 GCGAAGAGGA TTTTGTAGCC GAGCGCGAGG CGTCTGAACGCCGTCAGCAG 1501 GAAATGGAAG CCGCTGATAC CGAACCGTTT GCGGTGTGGCTGGAAAAACA 1551 CGCCtga (SEQ ID NO: 12) 41 FH12512877.6 Attorney Docket No.: NEX-16225 gshB (E. coli wild type) 1 MIKLGIVMDP IANINIKKDS SFAMLLEAQR RGYELHYMEM GDLYLINGEA 51 RAHTRTLNVK QNYEEWFSFV GEQDLPLADL DVILMRKDPP FDTEFIYATY 101 ILERAEEKGT LIVNKPQSLR DCNEKLFTAW FSDLTPETLV TRNKAQLKAF 151 WEKHSDIILK PLDGMGGASI FRVKEGDPNL GVIAETLTEH GTRYCMAQNY 201 LPAIKDGDKR VLVVDGEPVP YCLARIPQGG ETRGNLAAGG RGEPRPLTES 251 DWKIARQIGP TLKEKGLIFV GLDIIGDRLT EINVTSPTCI REIEAEFPVS 301 ITGMLMDAIE ARLQQQ (SEQ ID NO: 13) gshB (E. coli wild type) 1 atgATCAAGC TCGGCATCGT GATGGACCCC ATCGCAAACA TCAACATCAA 51 GAAAGATTCC AGTTTTGCTA TGTTGCTGGA AGCACAGCGT CGTGGTTACG 101 AACTTCACTA TATGGAGATG GGCGATCTGT ATCTGATCAA TGGTGAAGCC 151 CGCGCCCATA CCCGCACGCT GAACGTGAAG CAGAACTACG AAGAGTGGTT 201 TTCGTTCGTC GGTGAACAGG ATCTGCCGCT GGCCGATCTC GATGTGATCC 251 TGATGCGTAA AGACCCGCCG TTTGATACCG AGTTTATCTA CGCGACCTAT 301 ATTCTGGAAC GTGCCGAAGA GAAAGGGACG CTGATCGTTA ACAAGCCGCA 351 GAGCCTGCGC GACTGTAACG AGAAACTGTT TACCGCCTGG TTCTCTGACT 401 TAACGCCAGA AACGCTGGTT ACGCGCAATA AAGCGCAGCT AAAAGCGTTC 451 TGGGAGAAAC ACAGCGACAT CATTCTTAAG CCGCTGGACG GTATGGGCGG 501 CGCGTCGATT TTCCGCGTGA AAGAAGGCGA TCCAAACCTC GGCGTGATTG 551 CCGAAACCCT GACTGAGCAT GGCACTCGCT ACTGCATGGC GCAAAATTAC 601 CTGCCAGCCA TTAAAGATGG CGACAAACGC GTGCTGGTGG TGGATGGCGA 651 GCCGGTACCG TACTGCCTGG CGCGTATTCC GCAGGGGGGC GAAACCCGTG 701 GCAATCTGGC TGCCGGTGGT CGCGGTGAAC CTCGTCCGCT GACGGAAAGT 751 GACTGGAAAA TCGCCCGTCA GATCGGGCCG ACGCTGAAAG AAAAAGGGCT 801 GATTTTTGTT GGTCTGGATA TCATCGGCGA CCGTCTGACT GAAATTAACG 851 TCACCAGCCC AACCTGTATT CGTGAGATTG AAGCAGAGTT TCCGGTGTCG 901 ATCACCGGAA TGTTAATGGA TGCCATCGAA GCACGTTTAC AGCAGCAGta 951 a (SEQ ID NO: 14) In some embodiments, the microorganism is genetically engineered to express a sulfide quinone reductase (SQOR or SQR) enzyme, or homologs and variants thereof. In some embodiments, the engineered microorganism expresses SQR to sequester and store the 42 FH12512877.6 Attorney Docket No.: NEX-16225 H2S by-product (e.g., persulfides, polysulfides, elemental sulfur, or other sulfide by-products) intracellularly for the purpose of preventing the release of the sulfur / recycling of the sulfur back to H2S by the native microbiota and or host cells. SQOR: The protein encoded by this gene may function in mitochondria to catalyze the conversion of sulfide to persulfides, thereby decreasing toxic concentrations of sulfide. An example of sulfide quinone reductase (SQOR) enzyme is provided by the sequence of SEQ ID NO: 15 or 17, which is sulfide quinone reductase (SQOR) enzyme from Rhodobacter capsulatus or from Wolinella succinogenes, respectively. Homologues of sulfide quinone reductase (SQOR) enzyme from microorganisms other than Rhodobacter capsulatus or Wolinella succinogenes can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of sulfide quinone reductase (SQOR) enzyme in the instant invention are represented by UniProt entries: Q52722, Q9Y6N5, Q9R112, Q54DK1, Q8NFU3, Q12305, A0A812UN59, A0A813AHA6, B0BMT9, A0A670YA51, A0A6J0TFA8, A0A6P9D5C0, A0A8C7E7R8, A0A8D0ED51, A0A9F2QUP7, A0A670JN21, A0A6J1UR84, A0A8C5RDU1, A0AA97KN11, A0A8D0L849, A0A8I3Q5D3, F1QYT2, A0A1L8H0P4, A0A7K4Q091, 0A7K4RTG5, A0A7K4ZCV4, A0A7K5GD12, A0A7K5HF48, A0A7K5K611, A0A7K5VA50, A0A7K6HLE6, A0A7K6ME36, A0A7K6PUU7, A0A7K6V4E4, A0A7K6ZGM3, A0A7K7KUA5, A0A7K7T2M6, A0A7K8CQ51, A0A7K8GYD9, A0A7K8IJE8, A0A7K8JMC0, A0A7K8SFI3, A0A7K9Q8P3, A0A7K9T991, A0A7K9WQ83, A0A7L0I1X7, A0A7L1FC45, A0A7L1HXH9, A0A7L1KUS8, A0A7L1P467, A0A7L1WAV7, A0A7L2HWH9, A0A7L2L0W2, A0A7L3A9J9, A0A7L3M8H4, A0A7L3Q2A8, A0A7L3RR41, and A0A7L4CC90. An example of sulfide quinone reductase (SQOR) enzyme is provided by the amino acid sequence of SEQ ID NO: 15 or 17, which is cysteine synthase A from Rhodobacter capsulatus or Wolinella succinogenes, respectively and encoded by the nucleic acid sequence of SEQ ID NO: 16 or 18. The UniProt entries listed herein are incorporated by reference in their entireties. SQR (R. capsulatus) 1 MAHIVVLGAG LGGAIMAYEL REQVRKEDKV TVITKDPMYH FVPSNPWVAV 51 GWRDRKEITV DLAPTMARKN IDFIPVAAKR LHPAENRVEL ENGQSVSYDQ 101 IVIATGPELA FDEIEGFGPE GHTQSICHID HAEEARLAFD RFCENPGPIL 151 IGAAQGASCF GPAYEFTFIL DTALRKRKIR DKVPMTFVTS EPYVGHLGLD 43 FH12512877.6 Attorney Docket No.: NEX-16225 201 GVGDTKGLLE GNLRDKHIKW MTSTRIKRVE KGKMVVEEVT EDGTVKPEKE 251 LPFGYAMMLP AFRGIKALMG IEGLVNPRGF VIVDQHQQNP TFKNVFAVGV 301 CVAIPPIGPT PVPCGVPKTG FMIESMVTAT AHNIGRIVRG FEADEVGSWN 351 AVCLADFGDQ GIAFVAQPQI PPRNVNWSSQ GKWVHWAKEG FERYFMHKLR 401 RGTSETFYEK AAMKFLGIDK LKAVKKG (SEQ ID NO: 15) SQR (R. capsulatus) 1 atggctcata tcgtggttct gggtgccggt ttgggcggcg ccatcatggc 51 atatgaattg cgcgaacagg tgcgcaagga agacaaggtc accgtcatca 101 ccaaggaccc gatgtatcat ttcgtgccct cgaacccctg ggtggcggtg 151 ggctggcgcg accgcaagga gatcaccgtg gaccttgcgc cgacgatggc 201 gcgcaagaac atcgacttca tcccggtggc agcgaagcgc ctgcatccgg 251 cggaaaaccg ggtcgagctg gaaaacggcc agtcggtcag ctacgaccag 301 atcgtcatcg ccaccggccc ggaactggcc ttcgacgaga tcgagggctt 351 cggccccgag ggccacacgc aatcgatctg ccatatcgac catgccgagg 401 aggcgcgtct ggcctttgac cgcttttgcg aaaaccccgg cccgatcctc 451 atcggcgcgg cgcagggcgc cagctgcttc ggcccggctt acgaattcac 501 cttcatcctt gataccgcgc tgcgcaagcg caagatccgc gacaaggtgc 551 cgatgacctt cgtcacctcg gagccctatg tcgggcatct ggggctggac 601 ggggtgggcg acaccaaggg cctgctcgaa ggcaacctgc gcgacaagca 651 catcaaatgg atgacctcga cccggatcaa acgcgtcgaa aagggcaaga 701 tggtggtcga ggaggtgacc gaggacggca cggtcaagcc cgagaaagag 751 ctgcccttcg gctatgcgat gatgctgccc gcgttccgcg gcatcaaggc 801 gctgatgggg atcgaggggc tggtcaatcc gcgcggcttc gtcatcgtcg 851 atcagcacca gcagaacccg accttcaaga acgtcttcgc ggtcggcgtc 901 tgcgtggcga tcccgccgat cgggccgacg ccggtgccct gcggcgtgcc 951 gaagaccggc ttcatgatcg aaagcatggt caccgccacc gcccacaaca 1001 tcggccggat cgtgcgcggg tttgaggccg acgaggtcgg cagctggaac 1051 gccgtctgtc tggccgattt cggcgatcag ggcatcgcct ttgtcgcgca 1101 gccgcagatc ccgccgcgca acgtgaactg gtcgagccag ggcaaatggg 1151 tgcattgggc caaggagggg ttcgagcgct atttcatgca caagctgcgc 1201 cgcgggacct ccgagacctt ctatgaaaag gccgcgatga agtttctggg 1251 catcgacaag ctgaaggccg tcaaaaaggg atag (SEQ ID NO: 16) 44 FH12512877.6 Attorney Docket No.: NEX-16225 SQR (W. succinogenes) 1 MSSLDREWLE ALEQMDGELK KAGLSRRDAL KVLGLGGAAL ALPATAPRAH 51 AASNAKGKIV IIGAGLAGIT VASRLSHALS KPDITIIDGG DKVDYQPGYT 101 LIASGVYGPN DVTYERAGLI PSGAKWIKEY VKEIDAAGNS VTTTSGQKIT 151 YDYLVVATGL VTDYSMVKGL SESDVGRNGI ASIYTLPTCQ KAFGQIKEFV 201 NQGGVGLFTD PHTPIKCGGA PKKIQFLVDD YARKEGKHDK IKTIFLPNGG 251 TMFGVKEYAE MIERLYKEKG MEWKFKHNLV AIDPASKKAT FEYTYTVKGE 301 FDEVLGEHEL ITQKDNVVMD YDFIHVTPPM RAPKMVKDSE LSWKRGSASA 351 GGWMELVKET LQHPVYKNVF GLGDVAGIPM GKTGGSVRKQ APVLVENLIN 401 AMEGKEPTAQ YGGYTVCPLI VDYGRVAMLE FDWSATPKPS FPLDPSVPRW 451 VYWAMKVYML KPMTMIGMLK GYA (SEQ ID NO: 17) SQR (W. succinogenes) 1 atgtcctcac ttgataggga atggctagag gctttagagc agatggatgg 51 ggagctcaaa aaggcggggt tgagccgaag ggatgcgctc aaggttctag 101 ggcttggagg ggcggctctc gctctccctg cgaccgctcc cagggcgcac 151 gcggcgagta atgctaaagg gaagattgtc attattggag caggactcgc 201 aggaatcact gtggcatcgc gtctaagcca cgcccttagc aagcctgata 251 tcacgatcat tgatgggggc gataaggtcg attaccaacc tggatacaca 301 ttgattgcct cgggtgttta tgggcccaat gatgtcactt acgagcgtgc 351 aggactcatt cctagtggtg cgaagtggat caaagagtat gtcaaagaga 401 ttgatgcggc aggaaatagc gtcaccacca cctcaggtca aaagatcact 451 tatgactatc tcgtggttgc gacaggtttg gtgactgatt attcaatggt 501 taaaggtttg agcgaaagcg acgtgggtcg caatggaatc gcctctatct 551 atacgcttcc cacctgccaa aaggcctttg gccaaatcaa ggagtttgtc 601 aaccaggggg gtgtagggct tttcaccgac ccccatactc ctattaaatg 651 cggaggtgct cccaaaaaga ttcagtttct cgtggatgac tacgcccgaa 701 aagaggggaa acatgacaag ataaagacga tctttctgcc caatgggggg 751 acaatgtttg gggtcaaaga gtacgcagag atgattgaac gcctctacaa 801 agagaagggg atggagtgga aattcaagca caatctcgtg gcgatcgatc 851 ccgcttccaa aaaggcgacc tttgagtaca cctacacagt caagggagag 901 tttgatgagg tgttgggaga gcatgagctc attacccaaa aagataatgt 951 ggtgatggat tatgacttta tccatgtcac ccctccgatg agagccccca 1001 agatggttaa agattcggag ctctcttgga agaggggaag tgcatcagct 1051 gggggctgga tggagcttgt gaaggagacc ttgcaacacc ctgtctataa 45 FH12512877.6 Attorney Docket No.: NEX-16225 1101 aaatgtcttt ggtcttggtg atgtggcggg aatccccatg ggtaaaacag 1151 ggggaagcgt aaggaagcaa gcgcctgttt tggtggagaa tctcattaac 1201 gcgatggaag gcaaagagcc caccgctcaa tatggcggct acaccgtatg 1251 ccctctgatt gtcgattatg gtcgtgtggc gatgctagaa tttgactgga 1301 gcgccacacc caagccctcc ttccctcttg atccttcagt gcctaggtgg 1351 gtttattggg cgatgaaagt ctatatgctg aaacctatga ccatgattgg 1401 gatgcttaaa ggctacgcct aa (SEQ ID NO: 18) H2S Production Provided herein are microorganisms, systems and methods for modulating H2S. In certain aspects, the present disclosure provides genetically engineered microorganisms capable of producing H2S. For example, the microorganism described herein can converts L- cysteine to H2S and optionally converts glutathione to L-cysteine. In some embodiments, the microorganism is genetically engineered to express a peptidase T, or homologs and variants thereof. PepT is an enzyme that removes the N-terminal amino acid from tripeptides. An example of peptidase T is provided by the sequence of SEQ ID NO: 19, which is peptidase T from Escherichia coli. Homologues of peptidase T from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non- limiting examples of the homologs of peptidase T in the instant invention are represented by UniProt entries: P29745, P0C2T7, Q76HM5, P26311, Q9L4G1, Q84BV2, Q76HM7, P81207, Q21219, Q81WU4, Q835J5, Q6D4E3, P55179, Q38X92, A9VR36, Q5WK52, A7ZAB2, B5QXA9, P65805, Q4L4G8, Q6GIP8, Q8Y6B1, Q9CP05, A2RF89, B8ZPG1, P58794, Q64WS4, Q6GB87, Q8XPD8, Q92AM8, B7VSC8, B5BAE8, P65806, Q5HHS7, Q5LFT7, Q5PMK2, Q6LR24, Q7MDF5, Q87GX2, Q8NXM6, Q2YSI6, Q669P7, P0DD01, Q24VU3, Q5HQY6, Q5KZ39, Q636T5, Q8CXN0, A0Q3I1, A2RMN0, A3CNH0, A8Z018, B1HZ48, B1XA37, B4T3R6, C0ZDI3, C1FSB0, Q0SWT9, Q32EY5, Q97LS8, A0RHB6, A4INW9, A5UEI5, B1KV00, B4TFK5, B5FK77, B5XKT3, C1KW79, C5DAS5, Q1JHK2, Q1JMF5, Q83RR6, Q8CPZ6, A5UBV7, A7GAK0, A8AXT3, A8H6S3, A9MG86, B0TPD4, B1JI59, B1KHS7, B6ER23, B6I9K6, B8DDX7, C0Q764, C1CK88, P45172, Q1C6R3, Q3Z2Z2, A0KIP7, A7GR91, A8G0I7, A8ML45, and B1IBG7. An example of peptidase T is provided by the amino acid sequence of SEQ ID NO: 19, which is peptidase T from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 20. 46 FH12512877.6 Attorney Docket No.: NEX-16225 The UniProt entries listed herein are incorporated by reference in their entireties. pepT (E. coli) 1 MDKLLERFLN YVSLDTQSKA GVRQVPSTEG QWKLLHLLKE QLEEMGLINV 51 TLSEKGTLMA TLPANVPGDI PAIGFISHVD TSPDCSGKNV NPQIVENYRG 101 GDIALGIGDE VLSPVMFPVL HQLLGQTLIT TDGKTLLGAD DKAGIAEIMT 151 ALAVLQQKKI PHGDIRVAFT PDEEVGKGAK HFDVDAFDAR WAYTVDGGGV 201 GELEFENFNA ASVNIKIVGN NVHPGTAKGV MVNALSLAAR IHAEVPADES 251 PEMTEGYEGF YHLASMKGTV ERADMHYIIR DFDRKQFEAR KRKMMEIAKK 301 VGKGLHPDCY IELVIEDSYY NMREKVVEHP HILDIAQQAM RDCDIEPELK 351 PIRGGTDGAQ LSFMGLPCPN LFTGGYNYHG KHEFVTLEGM EKAVQVIVRI 401 AELTAQRK (SEQ ID NO: 19) pepT (E. coli) 1 atgGATAAAC TACTTGAGCG ATTTTTGAAC TACGTGTCTC TGGATACCCA 51 ATCAAAAGCA GGGGTGAGAC AGGTTCCCAG CACGGAAGGC CAATGGAAGT 101 TATTGCATCT GCTGAAAGAG CAGCTCGAAG AGATGGGGCT TATCAATGTG 151 ACCTTAAGTG AGAAGGGCAC TTTGATGGCG ACGTTACCGG CTAACGTCCC 201 TGGCGATATC CCGGCGATTG GCTTTATTTC TCATGTGGAT ACCTCACCGG 251 ATTGCAGCGG CAAAAATGTG AATCCGCAAA TTGTTGAAAA CTATCGCGGT 301 GGCGATATTG CGCTGGGTAT CGGCGATGAA GTTTTATCAC CGGTTATGTT 351 CCCGGTGCTG CATCAGCTAC TGGGTCAGAC GCTGATTACC ACCGATGGTA 401 AAACCTTGTT AGGTGCCGAT GACAAAGCAG GTATTGCAGA AATCATGACC 451 GCGCTGGCGG TATTGCAACA GAAAAAAATT CCGCATGGTG ATATTCGCGT 501 CGCCTTTACC CCGGATGAAG AAGTGGGCAA AGGGGCGAAA CATTTTGATG 551 TTGACGCCTT CGATGCCCGC TGGGCTTACA CTGTTGATGG TGGTGGCGTA 601 GGCGAACTGG AGTTTGAAAA CTTCAACGCC GCGTCGGTCA ATATCAAAAT 651 TGTCGGTAAC AATGTTCATC CGGGCACGGC GAAAGGAGTG ATGGTAAATG 701 CGCTGTCGCT GGCGGCACGT ATTCATGCGG AAGTTCCGGC GGATGAAAGC 751 CCGGAAATGA CAGAAGGCTA TGAAGGTTTC TATCATCTGG CGAGCATGAA 801 AGGCACCGTT GAACGGGCCG ATATGCACTA CATCATCCGT GATTTCGACC 851 GTAAACAGTT TGAAGCGCGT AAACGTAAAA TGATGGAGAT CGCCAAAAAA 901 GTGGGCAAAG GGTTACATCC TGATTGCTAC ATTGAACTGG TGATTGAAGA 951 CAGTTACTAC AATATGCGCG AGAAAGTGGT TGAGCATCCG CATATTCTCG 1001 ATATCGCCCA GCAGGCGATG CGCGATTGCG ATATTGAACCGGAACTGAAA 47 FH12512877.6 Attorney Docket No.: NEX-16225 1051 CCGATCCGCG GTGGTACCGA CGGCGCGCAG TTGTCGTTTA TGGGATTACC 1101 GTGCCCGAAC CTGTTCACTG GCGGTTACAA CTATCATGGT AAGCATGAGT 1151 TTGTGACTCT GGAAGGTATG GAAAAAGCGG TGCAGGTGAT CGTCCGTATT 1201 GCCGAGTTAA CGGCGCAACG GAAGtaa (SEQ ID NO: 20) In some embodiments, the microorganism is genetically engineered to express a peptidase B, or homologs and variants thereof. PepB is a metallopeptidase belonging to the M17 family and is classified as a leucine aminopeptidase (LAP) and has cysteinylglycine dipeptidase activity based on sequence and activity. An example of peptidase B is provided by the sequence of SEQ ID NO: 21, which is peptidase B from Escherichia coli. Homologues of peptidase B from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non- limiting examples of the homologs of peptidase B in the instant invention are represented by UniProt entries: P37095, Q9RF52, Q53778, Q6D266, Q8E0C9, A7MU37, B7VJT3, Q667Y8, Q7MNF5, Q9CM16, A8A329, B1LNH8, Q1C5H7, Q8DEZ4, Q8Z4N3, A4TMU7, B5FR78, B6I595, Q31XW7, Q32D41, Q57LH5, Q9KTX5, B5R595, Q7N231, Q87S21, A9N1Y3, A9R811, B4T0R5, C0PYL4, A9MHK1, B1IWD8, B1JRZ6, B2K9R0, C6DBI4, Q83QK5, B1XAZ8, B7N6B0, C4ZX98, Q1R8K9, Q3YZ29, Q1CKA2, P58474, P58475, A7MGW9, Q4QM33, Q9HEZ3, Q8FF47, A8AD60, B7MYF7, B5RD05, and B2TXU8. An example of peptidase B is provided by the amino acid sequence of SEQ ID NO: 21, which is peptidase B from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 22. The UniProt entries listed herein are incorporated by reference in their entireties. pepB (E. coli) 1 MTEAMKITLS TQPADARWGE KATYSINNDG ITLHLNGADD LGLIQRAARK 51 IDGLGIKHVQ LSGEGWDADR CWAFWQGYKA PKGTRKVVWP DLDDAQRQEL 101 DNRLMIIDWV RDTINAPAEE LGPSQLAQRA VDLISNVAGD RVTYRITKGE 151 DLREQGYMGL HTVGRGSERS PVLLALDYNP TGDKEAPVYA CLVGKGITFD 201 SGGYSIKQTA FMDSMKSDMG GAATVTGALA FAITRGLNKR VKLFLCCADN 251 LISGNAFKLG DIITYRNGKK VEVMNTDAEG RLVLADGLID ASAQKPEMII 301 DAATLTGAAK TALGNDYHAL FSFDDALAGR LLASAAQENE PFWRLPLAEF 48 FH12512877.6 Attorney Docket No.: NEX-16225 351 HRSQLPSNFA ELNNTGSAAY PAGASTAAGF LSHFVENYQQ GWLHIDCSAT 401 YRKAPVEQWS AGATGLGVRT IANLLTA (SEQ ID NO: 21) pepB (E. coli) 1 atgACAGAAG CGATGAAGAT TACCCTCTCT ACCCAACCTG CCGACGCGCG 51 CTGGGGAGAA AAAGCAACTT ACAGCATTAA TAATGACGGC ATTACCCTGC 101 ATTTGAACGG GGCAGACGAT CTGGGGCTGA TCCAGCGTGC GGCGCGCAAG 151 ATTGACGGTC TGGGCATCAA GCATGTTCAG TTAAGCGGTG AAGGCTGGGA 201 TGCGGATCGC TGCTGGGCAT TCTGGCAAGG TTACAAAGCC CCGAAAGGCA 251 CGCGTAAAGT GGTGTGGCCG GATCTGGACG ATGCCCAGCG CCAGGAACTG 301 GATAACCGCC TGATGATCAT CGACTGGGTG CGTGACACCA TCAACGCACC 351 GGCAGAAGAA TTGGGACCAT CGCAACTGGC ACAGCGTGCT GTTGATCTGA 401 TCAGCAACGT CGCGGGCGAT CGTGTGACTT ATCGGATCAC CAAAGGCGAA 451 GATCTGCGTG AGCAAGGTTA TATGGGGCTG CACACAGTCG GACGCGGTTC 501 AGAACGTTCT CCGGTATTGC TGGCGCTGGA TTACAACCCA ACTGGCGATA 551 AAGAAGCGCC AGTGTACGCG TGCCTGGTAG GTAAAGGTAT CACTTTTGAC 601 TCCGGCGGCT ACAGCATCAA ACAGACTGCG TTTATGGACT CGATGAAGTC 651 GGACATGGGC GGCGCGGCAA CGGTTACCGG GGCGCTGGCA TTTGCCATTA 701 CGCGCGGACT GAACAAGCGC GTGAAGCTGT TCCTCTGCTG TGCGGATAAC 751 CTGATTAGCG GCAATGCGTT CAAGCTGGGC GATATCATCA CCTATCGCAA 801 CGGTAAAAAA GTTGAAGTGA TGAACACTGA TGCCGAAGGG CGTCTGGTGC 851 TTGCCGATGG TCTGATTGAT GCCAGTGCGC AGAAACCGGA AATGATCATT 901 GATGCGGCGA CCCTCACCGG GGCGGCGAAA ACTGCGCTGG GTAATGATTA 951 TCACGCGCTG TTCAGTTTTG ACGATGCGCT GGCCGGTCGC TTGCTGGCGA 1001 GTGCCGCGCA GGAGAACGAA CCGTTCTGGC GTCTGCCGCT GGCGGAGTTC 1051 CACCGCAGCC AGCTGCCGTC TAACTTTGCC GAACTGAACA ATACCGGAAG 1101 CGCGGCGTAT CCGGCAGGCG CGAGCACGGC GGCGGGCTTC CTGTCGCACT 1151 TTGTTGAGAA CTATCAGCAA GGCTGGCTGC ATATCGACTG CTCGGCGACT 1201 TACCGTAAAG CGCCGGTTGA ACAGTGGTCT GCGGGCGCTA CGGGACTTGG 1251 TGTGCGCACG ATAGCTAATC TGTTAACGGC Gtaa (SEQ ID NO: 22) In some embodiments, the microorganism is genetically engineered to express a glutathione hydrolase, or homologs and variants thereof. 49 FH12512877.6 Attorney Docket No.: NEX-16225 ggt is an enzyme that hydrolyzes the gamma-glutamyl bond of extracellular reduced and oxidized glutathione, initiating their cleavage into glutamate, cysteine (cystine) and glycine. An example of glutathione hydrolase is provided by the sequence of SEQ ID NO: 23, which is glutathione hydrolase from Escherichia coli. Homologues of glutathione hydrolase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of glutathione hydrolase in the instant invention are represented by UniProt entries: P18956, P19440, P07314, P54422, Q60928, P20735, P63186, P36269, Q9QWE9, Q9UJ14, Q6P531, Q99JP7, Q99MZ4, Q9Z2A9, P36267, Q9I406, A0A193AUF6, D4B387, Q9LR30, Q9S7E9, O14194, Q9US04, Q0V8L2, Q6PDE7, A0A193AU77, Q6IE08, P74181, and A7YWM1. An example of glutathione hydrolase is provided by the amino acid sequence of SEQ ID NO: 23, which is glutathione hydrolase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 24. The UniProt entries listed herein are incorporated by reference in their entireties. ggT (E. coli) 1 MIKPTFLRRV AIAALLSGSC FSAAAAPPAP PVSYGVEEDV FHPVRAKQGM 51 VASVDATATQ VGVDILKEGG NAVDAAVAVG YALAVTHPQA GNLGGGGFML 101 IRSKNGNTTA IDFREMAPAK ATRDMFLDDQ GNPDSKKSLT SHLASGTPGT 151 VAGFSLALDK YGTMPLNKVV QPAFKLARDG FIVNDALADD LKTYGSEVLP 201 NHENSKAIFW KEGEPLKKGD TLVQANLAKS LEMIAENGPD EFYKGTIAEQ 251 IAQEMQKNGG LITKEDLAAY KAVERTPISG DYRGYQVYSM PPPSSGGIHI 301 VQILNILENF DMKKYGFGSA DAMQIMAEAE KYAYADRSEY LGDPDFVKVP 351 WQALTNKAYA KSIADQIDIN KAKPSSEIRP GKLAPYESNQ TTHYSVVDKD 401 GNAVAVTYTL NTTFGTGIVA GESGILLNNQ MDDFSAKPGV PNVYGLVGGD 451 ANAVGPNKRP LSSMSPTIVV KDGKTWLVTG SPGGSRIITT VLQMVVNSID 501 YGLNVAEATN APRFHHQWLP DELRVEKGFS PDTLKLLEAK GQKVALKEAM 551 GSTQSIMVGP DGELYGASDP RSVDDLTAGY (SEQ ID NO: 23) ggT (E. coli) 1 atgATAAAAC CGACGTTTTT ACGCCGGGTG GCCATTGCTG CTCTGCTCTC 51 AGGAAGTTGT TTTAGCGCCG CCGCCGCGCC TCCTGCGCCG CCCGTCTCGT 101 ATGGTGTGGA GGAAGATGTC TTCCACCCGG TACGCGCGAA ACAGGGAATG 151 GTAGCGTCTG TGGACGCCAC TGCCACTCAG GTGGGGGTGG ATATTCTCAA 50 FH12512877.6 Attorney Docket No.: NEX-16225 201 GGAGGGCGGG AATGCCGTTG ATGCCGCCGT GGCGGTGGGC TACGCGCTGG 251 CGGTAACGCA TCCGCAGGCA GGGAATCTGG GCGGTGGTGG TTTTATGTTA 301 ATCCGCTCGA AAAATGGCAA TACCACGGCT ATCGATTTCC GCGAAATGGC 351 ACCCGCCAAA GCGACCCGCG ATATGTTCCT CGATGATCAG GGCAACCCGG 401 ACAGCAAAAA ATCACTCACT TCGCATCTGG CTTCCGGCAC ACCGGGTACG 451 GTAGCAGGTT TCTCGCTGGC GCTGGATAAA TACGGCACCA TGCCGCTGAA 501 CAAAGTCGTG CAGCCCGCGT TTAAACTGGC ACGCGATGGT TTTATCGTTA 551 ACGACGCGCT GGCTGACGAT CTCAAAACCT ACGGTAGCGA AGTGTTGCCG 601 AATCACGAAA ACAGTAAAGC TATCTTCTGG AAAGAGGGCG AGCCGCTGAA 651 AAAGGGCGAC ACGCTGGTGC AGGCGAACCT GGCAAAGAGCCTGGAGATGA 701 TTGCTGAAAA CGGCCCGGAC GAATTCTATA AAGGCACGAT TGCGGAACAG 751 ATCGCCCAGG AGATGCAGAA AAACGGTGGC TTGATCACTA AAGAAGATTT 801 AGCAGCCTAT AAAGCGGTCG AACGCACTCC GATAAGCGGC GATTATCGCG 851 GGTATCAGGT TTACTCCATG CCACCGCCAT CCTCCGGCGG GATCCATATC 901 GTACAAATCC TCAATATTCT GGAAAACTTC GATATGAAGA AATACGGCTT 951 TGGCAGCGCC GATGCGATGC AAATCATGGC AGAAGCGGAG AAATACGCCT 1001 ACGCCGACCG CTCGGAATAT CTTGGCGACC CGGATTTTGT CAAAGTACCG 1051 TGGCAGGCGC TGACCAATAA AGCCTATGCC AAATCTATTG CCGATCAAAT 1101 TGATATCAAT AAAGCGAAGC CATCCAGCGA AATTCGCCCC GGCAAGCTTG 1151 CGCCTTATGA GAGTAATCAA ACTACCCATT ACTCAGTGGT GGATAAAGAT 1201 GGTAACGCGG TGGCGGTGAC CTATACGCTG AACACCACCT TCGGTACGGG 1251 CATTGTCGCG GGCGAGAGCG GTATTCTGCT TAATAACCAG ATGGATGATT 1301 TCTCCGCCAA ACCGGGCGTA CCGAACGTTT ACGGGCTGGT GGGCGGTGAT 1351 GCCAACGCCG TCGGGCCGAA CAAACGCCCG CTGTCGTCGA TGTCGCCGAC 1401 CATTGTGGTG AAAGACGGTA AAACCTGGCT GGTTACCGGTAGCCCAGGCG 1451 GTAGCCGGAT CATCACTACA GTGCTGCAAA TGGTGGTGAA TAGCATCGAT 1501 TATGGCTTGA ACGTCGCCGA AGCGACCAAT GCGCCGCGTT TCCACCATCA 1551 GTGGTTGCCG GACGAGCTGC GTGTCGAAAA AGGGTTTAGCCCGGATACGC 1601 TCAAGCTGCT GGAAGCAAAAGGTCAGAAAGTGGCGCTGAAAGAGGCGATG 1651 GGCAGTACAC AAAGCATTAT GGTTGGGCCG GACGGTGAGTTGTACGGCGC 1701 ATCCGACCCG CGCTCGGTGG ATGATTTAAC GGCGGGGTAC taa (SEQ ID NO: 24) In some embodiments, the microorganism is genetically engineered to express a desulfidase (3'-5' exoribonuclease), or homologs and variants thereof. 51 FH12512877.6 Attorney Docket No.: NEX-16225 yhaM is a cysteine desulfidase that breaks down cysteine into pyruvate, hydrogen sulfide, and ammonium. An example of desulfidase is provided by the sequence of SEQ ID NO: 25, which is desulfidase from Escherichia coli. Homologues of desulfidase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non- limiting examples of the homologs of desulfidase in the instant invention are represented by UniProt entries: P42626, O07521, Q9KDN6, Q5WHU5, A9VI37, A7Z305, Q929F3, Q8Y556, Q5L299, Q63EZ0, Q8CUG1, A0RAN0, C3LCZ8, B9ISF7, Q71XE5, Q6HME9, C1KXH5, C3P2S0, Q65LT6, Q81H06, C5D6L2, A7GLX6, Q81U72, A0AKX3, B7HFZ0, B7IK95, B7HYS8, A8FBK3, Q8XAF6, B7JCU0, C1EKC8, Q73CF4, Q58431, P42628, O34441, B5BGF2, Q8ZLW5, Q5PCB2, B5QZR6, A9MPR6, B5FHX2, Q1R6M3, A9N623, B1IRK5, B4T6A7, B4TIW6, C4ZR24, Q31WS0, Q57JM2, Q8Z3K8, B1LFL2, B1XGS5, Q3YXB9, A8A4S3, B4TVX2, B6I485, B7ND98, C0PZ11, 32BK8, Q83JI4, B5REJ4, Q8FDC6, B7MB40, B7N0B1, B5F6P5, A7ZS00, B7LH44, B7UJ14, Q0TCZ4, B2U0A8, Q0T0F8, A0A6M4JH18, A1AG22, B7M017, B7NJX7, B5YS00, A0A248TDQ1, A0A5C0WC92, A0A0H3E150, A0A378MFG5, A0A3Q0NHP8, A0A7U5AUZ7, A0A223KLU0, A0A0E0UY02, A0A3G6UPN3, A0A7G7UAS3, and A0A0M3RFJ7. An example of desulfidase is provided by the amino acid sequence of SEQ ID NO: 25, which is desulfidase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 26. The UniProt entries listed herein are incorporated by reference in their entireties. yhaM (E. coli) 1 MFDSTLNPLW QRYILAVQEE VKPALGCTEP ISLALAAAVA AAELEGPVER 51 VEAWVSPNLM KNGLGVTVPG TGMVGLPIAA ALGALGGNAN AGLEVLKDAT 101 AQAIADAKAL LAAGKVSVKI QEPCDEILFS RAKVWNGEKW ACVTIVGGHT 151 NIVHIETHDG VVFTQQACVA EGEQESPLTV LSRTTLAEIL KFVNEVPFAA 201 IRFILDSAKL NCALSQEGLS GKWGLHIGAT LEKQCERGLL AKDLSSSIVI 251 RTSAASDARM GGATLPAMSN SGSGNQGITA TMPVVVVAEH FGADDERLAR 301 ALMLSHLSAI YIHNQLPRLS ALCAATTAAM GAAAGMAWLV DGRYETISMA 351 ISSMIGDVSG MICDGASNSC AMKVSTSASA AWKAVLMALD DTAVTGNEGI 401 VAHDVEQSIA NLCALASHSM QQTDRQIIEI MASKAR (SEQ ID NO: 25) yhaM (E. coli) 1 atgTTTGATT CGACTTTAAA TCCGTTATGG CAGCGTTACA TCCTCGCCGT 52 FH12512877.6 Attorney Docket No.: NEX-16225 51 TCAGGAGGAA GTAAAACCGG CGCTGGGATG TACTGAACCG ATTTCACTGG 101 CGCTGGCGGC GGCGGTTGCT GCGGCAGAAC TGGAAGGTCC GGTTGAACGT 151 GTAGAAGCCT GGGTTTCGCC AAATCTGATG AAGAACGGTC TGGGCGTCAC 201 CGTTCCCGGC ACGGGAATGG TGGGGCTGCC GATTGCGGCG GCGCTGGGGG 251 CGTTAGGTGG AAATGCCAAC GCCGGGCTGG AAGTGCTGAA AGACGCAACA 301 GCGCAGGCAA TTGCCGATGC CAAAGCACTG CTGGCGGCGG GGAAAGTCTC 351 CGTTAAGATC CAGGAACCTT GCGATGAAAT CCTCTTCTCA CGCGCCAAAG 401 TCTGGAACGG TGAGAAGTGG GCGTGTGTCA CCATCGTCGG CGGGCATACC 451 AACATTGTGC ATATCGAGAC GCACGATGGT GTGGTGTTTA CCCAGCAGGC 501 GTGTGTGGCA GAGGGCGAGC AAGAGTCTCC GCTGACGGTG CTTTCCAGAA 551 CGACGCTGGC TGAGATCCTG AAGTTCGTCA ATGAAGTCCC GTTTGCGGCG 601 ATCCGCTTTA TTCTCGATTC CGCGAAGCTA AATTGTGCGT TATCGCAGGA 651 AGGTTTGAGC GGTAAGTGGG GGCTGCATAT TGGCGCGACG CTGGAAAAAC 701 AGTGCGAGCG CGGTTTGCTG GCGAAAGATC TCTCTTCATC CATTGTGATT 751 CGTACCAGCG CGGCATCCGA TGCGCGTATG GGCGGCGCTA CGCTTCCGGC 801 TATGAGTAAC TCCGGCTCGG GTAACCAGGG GATTACCGCA ACAATGCCTG 851 TGGTGGTGGT AGCAGAACAC TTCGGAGCGG ATGATGAACG GCTGGCGCGT 901 GCGCTGATGC TTTCGCATTT GAGCGCAATT TACATCCATA ACCAGTTACC 951 GCGTTTGTCT GCGCTGTGTG CCGCAACGAC CGCAGCAATG GGGGCCGCCG 1001 CCGGGATGGC ATGGCTGGTG GATGGGCGTT ATGAAACCAT CTCGATGGCG 1051 ATCAGCAGTA TGATCGGCGA TGTCAGCGGC ATGATTTGCG ATGGTGCGTC 1101 GAACAGCTGC GCGATGAAGG TTTCGACCAG TGCTTCGGCTGCGTGGAAAG 1151 CGGTGTTAAT GGCGCTGGAT GATACCGCCG TGACCGGCAA TGAAGGGATT 1201 GTGGCGCATG ATGTTGAGCA GTCGATTGCC AACCTGTGTG CGTTAGCAAG 1251 CCATTCGATG CAGCAAACGG ATCGGCAGAT TATCGAGATTATGGCGAGCA 1301 AGGCCAGAta a (SEQ ID NO: 26) In some embodiments, the microorganism is genetically engineered to express a L- cysteine importer, or homologs and variants thereof. yhaO is a L-cysteine importer and is part of a bicistronic operon with YhaM, a L- cysteine desulfidase. Permeases are membrane transport proteins that allow specific molecules to move in or out of cells. An example of L-cysteine importer is provided by the sequence of SEQ ID NO: 27, which is serine permease from Escherichia coli. Homologues of L-cysteine importer from 53 FH12512877.6 Attorney Docket No.: NEX-16225 microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of L-cysteine importers in the instant invention are represented by UniProt entries: P42628, O07522, Q8XAF5, P0ACJ5, P42626, A0A166FB33, A0A223YZZ4, A0A2U1S865, A0A166BYK2, A0A166FBN6, A0A2H5V8N4, A0A2H6JWJ8, A0A2H6GWE9, A0A315XMS1, A0A2A2HC94, A0A1V5P8A9, A0A2H5YWJ3, and A0A2H6AP10. An example of L-cysteine importer is provided by the amino acid sequence of SEQ ID NO: 27, which is L-cysteine importer from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 28. The UniProt entries listed herein are incorporated by reference in their entireties. yhaO (E. coli) 1 MEIASNKGVI ADASTPAGRA GMSESEWREA IKFDSTDTGW VIMSIGMAIG 51 AGIVFLPVQV GLMGLWVFLL SSVIGYPAMY LFQRLFINTL AESPECKDYP 101 SVISGYLGKN WGILLGALYF VMLVIWMFVY STAITNDSAS YLHTFGVTEG 151 LLSDSPFYGL VLICILVAIS SRGEKLLFKI STGMVLTKLL VVAALGVSMV 201 GMWHLYNVGS LPPLGLLVKN AIITLPFTLT SILFIQTLSP MVISYRSREK 251 SIEVARHKAL RAMNIAFGIL FVTVFFYAVS FTLAMGHDEA VKAYEQNISA 301 LAIAAQFISG DGAAWVKVVS VILNIFAVMT AFFGVYLGFR EATQGIVMNI 351 LRRKMPAEKI NENLVQRGIM IFAILLAWSA IVLNAPVLSF TSICSPIFGM 401 VGCLIPAWLV YKVPALHKYK GMSLYLIIVT GLLLCVSPFL AFS (SEQ ID NO: 27) yhaO (E. coli) 1 atgGAAATTG CATCGAATAA AGGCGTCATT GCAGACGCTT CGACCCCGGC 51 GGGTCGTGCT GGAATGAGTG AGAGCGAGTG GCGAGAAGCG ATCAAATTCG 101 ACAGTACTGA CACCGGCTGG GTGATTATGA GTATCGGGAT GGCGATTGGC 151 GCGGGGATTG TTTTTCTCCC GGTGCAGGTC GGTTTGATGG GATTGTGGGT 201 ATTTTTGCTC TCATCGGTGA TTGGTTACCC GGCAATGTAT CTGTTTCAGC 251 GATTGTTTAT TAATACGCTG GCAGAATCAC CAGAATGTAA AGATTACCCG 301 AGCGTCATTA GCGGTTATTT AGGTAAAAAC TGGGGCATCC TGTTAGGTGC 351 GCTCTATTTC GTAATGCTGG TGATTTGGAT GTTCGTCTAT TCCACCGCCA 401 TCACCAACGA TAGTGCTTCC TACCTGCATA CCTTCGGCGT GACGGAAGGG 451 TTGCTGTCAG ACAGTCCCTT TTATGGTCTG GTACTGATTT GCATTCTGGT 501 GGCGATCTCC TCACGCGGCG AGAAATTGTT ATTCAAAATT TCGACCGGCA 54 FH12512877.6 Attorney Docket No.: NEX-16225 551 TGGTGCTGAC CAAGCTGCTG GTGGTCGCGG CGCTGGGCGT GTCGATGGTG 601 GGAATGTGGC ATCTGTATAA CGTCGGTTCG CTACCGCCGC TGGGGCTGCT 651 GGTGAAAAAC GCCATTATTA CGCTGCCGTT TACCCTGACG TCGATTCTGT 701 TTATCCAGAC GTTAAGTCCG ATGGTGATCT CTTATCGCTC GCGGGAAAAA 751 TCAATTGAAG TGGCGCGGCA TAAAGCATTG CGGGCAATGA ATATCGCGTT 801 TGGCATTTTG TTTGTCACCG TCTTTTTCTA CGCCGTGTCG TTCACGCTGG 851 CGATGGGACA TGACGAAGCG GTAAAAGCCT ATGAGCAGAA TATTTCCGCG 901 CTGGCGATTG CCGCACAGTT TATTAGCGGT GACGGCGCAG CGTGGGTGAA 951 AGTGGTCAGC GTCATTCTCA ATATCTTTGC TGTCATGACT GCATTCTTTG 1001 GCGTCTATTT AGGCTTTCGC GAAGCAACGC AAGGGATCGT AATGAACATC 1051 CTGCGTCGCA AGATGCCTGC CGAGAAGATT AACGAAAATC TCGTTCAGCG 1101 CGGCATCATG ATTTTCGCCA TTTTGCTGGC CTGGAGCGCC ATCGTACTGA 1151 ACGCACCGGT GTTGAGCTTC ACCTCTATCT GTAGCCCGAT TTTCGGCATG 1201 GTAGGGTGCC TGATCCCGGC GTGGCTGGTT TACAAAGTAC CAGCATTGCA 1251 CAAATACAAA GGGATGTCTC TGTACCTGAT TATCGTCACT GGTTTGTTGC 1301 TGTGTGTTTC TCCGTTCCTG GCATTTTCTt ga (SEQ ID NO: 28) In some embodiments, the microorganism is genetically engineered to express a sulfite reductase, or homologs and variants thereof. CysI contains one siroheme and one 4-Fe-4S iron-sulfur center per chain. CysI is a gene that encodes the beta chain of the sulfite reductase complex. CysJ is the flavin or alpha subunit of sulfite reductase (SiR), an enzyme that plays a key role in the sulfur cycle. An example of sulfite reductase (CysI) is provided by the sequence of SEQ ID NO: 29, which is sulfite reductase from Escherichia coli. Homologues of sulfite reductase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of sulfite reductase (CysI) in the instant invention are represented by UniProt entries: P17846, P17845, Q9JS33, O32213, Q8VSR0, Q8KQT8, Q6D1A2, Q7VQH1, B5FGI9, Q9KF75, Q5WKE7, P52673, A7MSZ7, A7Z8R5, B7VI85, Q5NRM2, Q66ED3, Q9JUD9, A1KU05, A9IT77, P57502, Q65T54, Q6LM59, Q82W45, Q8P608, B4F234, B5BEZ8, Q2P0H2, Q4L9F1, Q2NVN3, Q5HKZ7, Q7N8L5, Q8PHC8, A0KNL0, A4IMT6, A8A3P4, A8FZY7, B1LQ86, B5FTU2, B8D7V7, C4ZZR7, Q0HFL7, Q0HYB3, Q1D9W9, Q1LTP2, Q1QU16, Q31XM5, and Q32CG4. 55 FH12512877.6 Attorney Docket No.: NEX-16225 An example of sulfite reductase (CysI) is provided by the amino acid sequence of SEQ ID NO: 29, which is sulfite reductase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 30. The UniProt entries listed herein are incorporated by reference in their entireties. cysI (E. coli) 1 MSEKHPGPLV VEGKLTDAER MKHESNYLRG TIAEDLNDGL TGGFKGDNFL 51 LIRFHGMYQQ DDRDIRAERA EQKLEPRHAM LLRCRLPGGV ITTKQWQAID 101 KFAGENTIYG SIRLTNRQTF QFHGILKKNV KPVHQMLHSV GLDALATAND 151 MNRNVLCTSN PYESQLHAEA YEWAKKISEH LLPRTRAYAE IWLDQEKVAT 201 TDEEPILGQT YLPRKFKTTV VIPPQNDIDL HANDMNFVAI AENGKLVGFN 251 LLVGGGLSIE HGNKKTYART ASEFGYLPLE HTLAVAEAVV TTQRDWGNRT 301 DRKNAKTKYT LERVGVETFK AEVERRAGIK FEPIRPYEFT GRGDRIGWVK 351 GIDDNWHLTL FIENGRILDY PARPLKTGLL EIAKIHKGDF RITANQNLII 401 AGVPESEKAK IEKIAKESGL MNAVTPQREN SMACVSFPTC PLAMAEAERF 451 LPSFIDNIDN LMAKHGVSDE HIVMRVTGCP NGCGRAMLAE VGLVGKAPGR 501 YNLHLGGNRI GTRIPRMYKE NITEPEILAS LDELIGRWAK EREAGEGFGD 551 FTVRAGIIRP VLDPARDLWD (SEQ ID NO: 29) cysI (E. coli) 1 atgAGCGAAA AACATCCAGG GCCTTTAGTG GTCGAAGGAA AACTGACAGA 51 CGCCGAGCGC ATGAAGCATG AAAGCAACTA CCTGCGCGGC ACCATTGCGG 101 AAGATTTAAA CGACGGTCTG ACCGGCGGCT TTAAGGGCGA CAACTTCCTG 151 CTGATTCGCT TCCACGGCAT GTATCAGCAG GATGACCGCG ACATCCGCGC 201 CGAACGTGCT GAACAGAAGC TGGAGCCGCG CCACGCGATG CTGCTTCGCT 251 GTCGTCTGCC GGGTGGGGTG ATTACCACTA AACAGTGGCA GGCGATCGAC 301 AAATTTGCCG GTGAAAACAC CATCTATGGC AGCATTCGCC TGACCAACCG 351 CCAGACGTTT CAGTTCCACG GCATTCTGAA AAAGAACGTC AAACCGGTGC 401 ACCAGATGCT GCACTCGGTC GGTCTTGATG CGCTGGCGAC AGCTAACGAC 451 ATGAACCGTA ACGTACTCTG CACCTCGAAC CCTTACGAGT CGCAGCTGCA 501 CGCGGAAGCG TACGAGTGGG CGAAGAAGAT TTCTGAGCAT CTGTTGCCTC 551 GTACCCGCGC GTATGCGGAG ATCTGGCTCG ACCAGGAAAA AGTCGCCACT 601 ACTGATGAAG AACCGATCCT CGGCCAGACC TACCTGCCGC GTAAATTCAA 651 AACCACGGTA GTGATCCCGC CACAGAACGA TATCGATCTG CACGCCAACG 701 ACATGAACTT CGTGGCGATC GCCGAAAACG GCAAGCTGGT GGGCTTTAAC 56 FH12512877.6 Attorney Docket No.: NEX-16225 751 CTGTTGGTGG GCGGTGGGCT TTCCATCGAA CACGGCAACA AGAAAACCTA 801 CGCCCGCACC GCGAGTGAGT TTGGCTATCT GCCGCTGGAG CATACGCTGG 851 CGGTGGCCGA AGCCGTCGTG ACAACTCAGC GTGACTGGGG TAACCGAACC 901 GATCGTAAAA ATGCCAAAAC CAAATACACG CTGGAGCGCG TGGGGGTTGA 951 GACGTTTAAA GCGGAAGTGG AGCGTCGCGC GGGGATCAAA TTTGAACCGA 1001 TCCGTCCATA TGAGTTCACC GGACGAGGCG ATCGTATTGG CTGGGTTAAG 1051 GGCATTGATG ATAACTGGCA CCTGACGCTG TTTATCGAAA ATGGTCGCAT 1101 CCTTGATTAT CCGGCGCGTC CGCTGAAAAC CGGCCTGCTG GAGATCGCGA 1151 AGATCCACAA AGGCGATTTC CGCATTACGG CGAACCAGAA TCTGATCATC 1201 GCCGGTGTACCGGAAAGCGAGAAAGCGAAGATCGAGAAGATCGCCAAAGA 1251 GAGCGGGTTA ATGAATGCCG TCACGCCGCA GCGTGAAAAC TCGATGGCTT 1301 GCGTGTCATT CCCGACTTGC CCGCTGGCGA TGGCGGAAGC AGAGCGTTTC 1351 CTGCCGTCTT TTATCGACAA CATCGATAAT TTAATGGCGA AACATGGTGT 1401 CAGCGATGAG CATATCGTGA TGCGTGTAAC AGGCTGCCCG AACGGTTGTG 1451 GTCGCGCGAT GCTGGCGGAA GTGGGCCTGG TGGGTAAAGCGCCGGGTCGC 1501 TACAACCTGC ATCTTGGCGG CAACCGCATT GGGACACGTA TCCCACGGAT 1551 GTATAAAGAA AACATCACCG AGCCGGAAAT CCTGGCGTCGCTTGATGAAC 1601 TGATAGGGCG CTGGGCGAAAGAGCGCGAAGCGGGTGAAGGCTTCGGCGAC 1651 TTTACGGTGC GTGCGGGCAT CATTCGCCCG GTGCTCGATC CGGCGCGTGA 1701 TTTGTGGGAT taa (SEQ ID NO: 30) An example of sulfite reductase (CysJ) is provided by the sequence of SEQ ID NO: 31, which is sulfite reductase from Escherichia coli. Homologues of sulfite reductase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of sulfite reductase (CysJ) in the instant invention are represented by UniProt entries: P38038, Q9JS45, O32214, P38039, Q8ZBN6, Q6D1A1, Q7VQH2, P52674, Q7N8L6, Q2NVN4, Q5PEH7, Q66ED4, Q65T53, Q31XM4, Q83QD9, Q8EAZ9, Q8K9D3, A4TPY5, A8A3P5, A9MF16, Q8Z458, A0KTH4, A9N2E6, Q8DCK2, A1KU06, P57503, Q5NRM1, Q87L90, Q9JUD8, Q6LM58, Q7MHA5, Q1CLS8, B1IU77, Q1C3Z0, Q1R7T4, Q3YY94, Q0HFL6, Q0HYB4, Q1LTP1, Q32CG3, Q57KH7, Q9KUX4, A7MJ63, Q5E841, Q8FEI7, Q8X7U1, A7FLZ0, and A7ZQK7. An example of sulfite reductase (CysJ) is provided by the amino acid sequence of SEQ ID NO: 31, which is sulfite reductase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 32. 57 FH12512877.6 Attorney Docket No.: NEX-16225 The UniProt entries listed herein are incorporated by reference in their entireties. cysJ (E. coli) 1 MTTQVPPSAL LPLNPEQLAR LQAATTDLTP TQLAWVSGYF WGVLNQQPAA 51 LAATPAPAAE MPGITIISAS QTGNARRVAE ALRDDLLAAK LNVKLVNAGD 101 YKFKQIASEK LLIVVTSTQG EGEPPEEAVA LHKFLFSKKA PKLENTAFAV 151 FSLGDSSYEF FCQSGKDFDS KLAELGGERL LDRVDADVEY QAAASEWRAR 201 VVDALKSRAP VAAPSQSVAT GAVNEIHTSP YSKDAPLVAS LSVNQKITGR 251 NSEKDVRHIE IDLGDSGMRY QPGDALGVWY QNDPALVKEL VELLWLKGDE 301 PVTVEGKTLP LNEALQWHFE LTVNTANIVE NYATLTRSET LLPLVGDKAK 351 LQHYAATTPI VDMVRFSPAQ LDAEALINLL RPLTPRLYSI ASSQAEVENE 401 VHVTVGVVRY DVEGRARAGG ASSFLADRVE EEGEVRVFIE HNDNFRLPAN 451 PETPVIMIGP GTGIAPFRAF MQQRAADEAP GKNWLFFGNP HFTEDFLYQV 501 EWQRYVKDGV LTRIDLAWSR DQKEKVYVQD KLREQGAELW RWINDGAHIY 551 VCGDANRMAK DVEQALLEVI AEFGGMDTEA ADEFLSELRV ERRYQRDVY (SEQ ID NO: 31) cysJ (E. coli) 1 atgACGACAC AGGTCCCACC TTCCGCGTTG CTTCCGTTGA ACCCGGAGCA 51 ACTGGCACGC CTTCAGGCGG CCACGACCGA TTTAACTCCC ACCCAGCTTG 101 CCTGGGTTTC TGGCTATTTC TGGGGCGTAC TCAATCAGCA GCCTGCTGCG 151 CTTGCAGCGA CGCCAGCGCC AGCCGCAGAA ATGCCGGGTA TAACTATTAT 201 CTCCGCCTCG CAAACCGGCA ATGCGCGCCG GGTTGCTGAA GCATTACGTG 251 ATGATTTATT AGCAGCAAAA CTGAACGTTA AGCTGGTGAA CGCGGGCGAC 301 TATAAATTCA AACAAATCGC CAGCGAAAAA CTGCTCATCG TAGTGACGTC 351 AACGCAAGGG GAAGGGGAAC CGCCGGAAGA AGCCGTCGCGCTGCATAAGT 401 TCCTGTTCTC CAAAAAAGCG CCAAAGCTGG AAAACACCGC GTTTGCCGTG 451 TTTAGCCTCG GCGATAGCTC TTATGAATTT TTCTGCCAGT CCGGGAAAGA 501 TTTCGACAGC AAGCTGGCGG AACTGGGTGG TGAACGCCTG CTCGACCGTG 551 TCGATGCCGA TGTTGAATAC CAGGCTGCTG CCAGCGAGTG GCGCGCCCGC 601 GTGGTTGATG CGCTTAAATC GCGTGCGCCT GTCGCGGCAC CTTCGCAATC 651 CGTCGCTACT GGCGCGGTAA ATGAAATCCA CACCAGCCCG TACAGCAAAG 701 ACGCGCCGCT GGTGGCTAGC CTCTCTGTTA ACCAGAAAAT TACCGGGCGT 751 AACTCTGAAA AAGACGTTCG CCATATCGAA ATTGACTTAG GTGACTCGGG 801 CATGCGTTAC CAGCCGGGTG ACGCGCTGGG CGTCTGGTAT CAGAACGATC 58 FH12512877.6 Attorney Docket No.: NEX-16225 851 CGGCACTGGT GAAAGAACTT GTCGAACTGC TGTGGCTGAA AGGCGATGAA 901 CCTGTCACCG TCGAGGGCAA AACGTTGCCT CTGAACGAAG CGCTACAGTG 951 GCACTTCGAA CTGACCGTCA ACACCGCCAA CATTGTTGAG AATTACGCCA 1001 CGCTTACCCG CAGTGAAACA CTGCTGCCGC TGGTGGGCGATAAAGCGAAG 1051 TTACAGCATT ACGCCGCGAC GACGCCGATT GTTGACATGG TGCGTTTCTC 1101 CCCGGCACAG CTTGATGCCG AAGCGCTAAT TAATCTGCTG CGCCCGCTGA 1151 CGCCGCGTCT GTATTCCATC GCCTCCTCGC AGGCGGAAGT CGAGAACGAA 1201 GTACACGTCA CCGTTGGTGT GGTGCGTTAC GACGTGGAAG GCCGCGCCCG 1251 TGCCGGTGGT GCCTCCAGCT TCCTCGCTGA CCGCGTGGAA GAAGAGGGCG 1301 AAGTCCGCGT ATTTATCGAA CATAACGATA ACTTCCGCCT GCCAGCCAAT 1351 CCAGAAACCC CGGTGATTAT GATTGGCCCA GGCACCGGTA TTGCGCCGTT 1401 CCGCGCCTTT ATGCAGCAAC GCGCCGCCGA CGAAGCGCCAGGTAAAAACT 1451 GGCTGTTCTT TGGTAATCCG CACTTTACGG AAGACTTCCT GTACCAGGTG 1501 GAGTGGCAGC GCTACGTCAA AGATGGCGTG CTGACACGTA TCGATCTTGC 1551 CTGGTCGCGC GATCAAAAAG AAAAAGTTTACGTACAAGACAAACTGCGCG 1601 AACAGGGCGC GGAGCTGTGG CGCTGGATCA ATGATGGTGC CCACATTTAT 1651 GTCTGCGGCG ACGCTAATCG CATGGCGAAA GACGTTGAGC AGGCACTTCT 1701 GGAAGTGATT GCCGAATTTG GTGGCATGGA CACCGAAGCGGCGGATGAAT 1751 TTTTAAGTGA GCTGCGCGTA GAGCGCCGTT ATCAGCGAGA TGTCTACtaa (SEQ ID NO: 32) In some embodiments, the microorganism is genetically engineered to express a siroheme synthetase, or homologs and variants thereof. CysG is the enzyme that produces siroheme, an iron-containing porphinoid that is essential for bacterial sulfur metabolism. An example of siroheme synthetase is provided by the sequence of SEQ ID NO: 33, which is siroheme synthetase from Escherichia coli. Homologues of siroheme synthetase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of siroheme synthetase in the instant invention are represented by UniProt entries: P0AEA8, Q65T49, Q820Q4, P25924, Q1H3L5, Q2Y6L7, P95370, Q74Y23, Q2KWB0, Q0A812, Q31GG8, P57001, Q606C9, Q6F8G6, Q7WB57, Q7WMM4, A1KU10, A9HZV6, P57500, Q7VQG9, Q9I0M7, B0BTC2, B0U4X0, B4TY38, C0Q0F3, C3JY53, Q32AZ8, Q3YWQ3, A1SRP9, A5CXE4, 59 FH12512877.6 Attorney Docket No.: NEX-16225 A5WEG6, B1X716, B5FJQ1, C4ZUM4, Q1LTP4, Q1R5R3, Q3SG32, Q9PF46, B5R2C7, Q5NRM4, Q5PLV8, Q2NVN0, Q7N8L2, Q7VZ77, Q87ZT0, B5BH22, and Q5FP95. An example of siroheme synthetase is provided by the amino acid sequence of SEQ ID NO: 33, which is siroheme synthetase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 34. The UniProt entries listed herein are incorporated by reference in their entireties. cysG (E. coli) 1 MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLEAGARLTV NALTFIPQFT 51 VWANEGMLTL VEGPFDETLL DSCWLAIAAT DDDTVNQRVS DAAESRRIFC 101 NVVDAPKAAS FIMPSIIDRS PLMVAVSSGG TSPVLARLLR EKLESLLPQH 151 LGQVARYAGQ LRARVKKQFA TMGERRRFWE KFFVNDRLAQ SLANADEKAV 201 NATTERLFSE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ QADIVVYDRL 251 VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK 301 GGDPFIFGRG GEELETLCHA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA 351 QSVRLVTGHL KTGGELDWEN LAAEKQTLVF YMGLNQAATI QEKLIAFGMQ 401 ADMPVALVEN GTSVKQRVVH GVLTQLGELA QQVESPALII VGRVVALRDK 451 LNWFSNH (SEQ ID NO: 33) cysG (E. coli) 1 atgGACCATC TCCCTATATT TTGTCAATTG CGCGACCGCG ACTGTCTGAT 51 CGTTGGCGGG GGCGATGTTG CTGAACGCAA AGCTCGGTTG CTGCTGGAAG 101 CTGGCGCTCG TTTGACCGTT AATGCGCTAA CCTTTATTCC CCAGTTCACC 151 GTATGGGCTA ATGAAGGCAT GCTCACACTG GTCGAGGGAC CGTTCGACGA 201 AACCCTCCTT GACAGTTGTT GGCTGGCGAT CGCGGCCACA GACGACGATA 251 CCGTTAACCA GCGCGTTAGC GACGCGGCGG AGTCACGCCG TATCTTTTGC 301 AACGTGGTGG ATGCGCCGAA AGCCGCCAGC TTTATCATGC CTTCGATTAT 351 TGACCGCAGT CCGCTGATGG TTGCCGTTTC GAGTGGCGGC ACCTCGCCGG 401 TGCTGGCGCG TCTGCTGCGC GAGAAACTGG AAAGTCTGCT GCCGCAGCAT 451 CTGGGGCAGG TTGCGCGCTA TGCCGGGCAA CTTCGCGCCC GAGTGAAAAA 501 GCAGTTTGCC ACCATGGGCG AGCGTCGTCG CTTCTGGGAA AAATTTTTCG 551 TTAATGACCG GCTGGCGCAG AGTCTGGCGA ATGCCGATGA GAAAGCGGTC 601 AACGCGACAA CCGAACGCCT GTTTAGCGAA CCGCTGGATC ACCGTGGCGA 651 AGTTGTGCTG GTTGGCGCCG GGCCGGGCGA TGCCGGACTG CTGACCCTGA 701 AAGGGTTGCA ACAAATCCAA CAGGCGGATA TCGTGGTCTA CGATCGCCTT 60 FH12512877.6 Attorney Docket No.: NEX-16225 751 GTTTCGGACG ACATTATGAA CCTGGTACGC CGCGATGCCG ATCGGGTTTT 801 TGTGGGGAAA CGCGCGGGGT ACCACTGCGT TCCCCAGGAG GAAATCAACC 851 AGATCCTGCT GCGTGAAGCG CAAAAAGGGA AACGCGTGGT ACGCCTGAAA 901 GGCGGCGATC CTTTTATCTT TGGGCGCGGC GGCGAAGAGC TGGAAACCCT 951 GTGTCATGCC GGGATTCCTT TCAGTGTAGT GCCGGGGATT ACCGCGGCTT 1001 CGGGCTGCTC GGCCTACTCG GGGATTCCGC TAACACATCG CGATTACGCC 1051 CAGAGCGTAC GTCTGGTTAC CGGGCACCTG AAAACCGGCGGCGAGCTGGA 1101 CTGGGAAAAC CTGGCGGCTG AAAAACAGAC CCTGGTGTTCTACATGGGGC 1151 TGAATCAGGC TGCGACAATC CAGGAAAAAC TGATCGCTTTCGGGATGCAG 1201 GCCGATATGC CGGTCGCGCT GGTAGAAAACGGGACCTCGGTGAAGCAACG 1251 CGTTGTTCAC GGGGTGCTGA CCCAGCTTGG GGAATTGGCG CAACAGGTCG 1301 AAAGCCCGGC GCTGATTATC GTCGGGCGCG TGGTAGCCTT GCGCGATAAA 1351 TTGAATTGGT TCTCAAATCA TTAA (SEQ ID NO: 34) Gene Knock out In some embodiments, the engineered microorganism lacks native DNA-binding transcriptional activator DecR (decR), iscS (cysteine desulfurase), yhaM (L-cysteine desulfidase) and / or yhaO (L-cysteine importer). iscS is cysteine desulfurase, which catalyzes the transfer of sulfur and selenium from cysteine and selenocysteine to a range of recipients. An example of cysteine desulfurase is provided by the sequence of SEQ ID NO: 35, which is cysteine desulfurase from Escherichia coli. Homologues of cysteine desulfurase from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of cysteine desulfurase in the instant invention are represented by UniProt entries: P0A6B7, O31269, P0A6B9, O54055, P9WQ71, Q6D259, B0VD51, B5R5A2, Q9HXI8, A7MU48, B7VJS6, B5BAW6, P57795, Q65RS7, Q7MNG2, Q5PNG1, Q60C64, Q7N224, Q87S28, Q8ZN40, B0VNW2, Q68WP6, Q9JTX0, A1KUK1, B4EZU8, P57657, P57803, Q6LU62, Q9JYY0, Q9ZD60, A0KJ32, A1AWM1, A8EYH9, A9N1X5, B8DZS1, C4L7K2, Q1RHY6, Q4UL77, Q8DEY7, Q3IFI3, A0KXJ0, A5CWM6, A8A336, A8FXA5, A8GNU0, A8H2M6, and A9MHJ4. An example of cysteine desulfurase is provided by the amino acid sequence of SEQ ID NO: 35, which is cysteine desulfurase from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 36. The UniProt entries listed herein are incorporated by reference in their entireties. 61 FH12512877.6 Attorney Docket No.: NEX-16225 iscS (E. coli) 1 MKLPIYLDYS ATTPVDPRVA EKMMQFMTMD GTFGNPASRS HRFGWQAEEA 51 VDIARNQIAD LVGADPREIV FTSGATESDN LAIKGAANFY QKKGKHIITS 101 KTEHKAVLDT CRQLEREGFE VTYLAPQRNG IIDLKELEAA MRDDTILVSI 151 MHVNNEIGVV QDIAAIGEMC RARGIIYHVD ATQSVGKLPI DLSQLKVDLM 201 SFSGHKIYGP KGIGALYVRR KPRVRIEAQM HGGGHERGMR SGTLPVHQIV 251 GMGEAYRIAK EEMATEMERL RGLRNRLWNG IKDIEEVYLN GDLEHGAPNI 301 LNVSFNYVEG ESLIMALKDL AVSSGSACTS ASLEPSYVLR ALGLNDELAH 351 SSIRFSLGRF TTEEEIDYTI ELVRKSIGRL RDLSPLWEMY KQGVDLNSIE 401 WAHH (SEQ ID NO: 35) iscS (E. coli) 1 atgAAATTAC CGATTTATCT CGACTACTCC GCAACCACGC CGGTGGACCC 51 GCGTGTTGCC GAGAAAATGA TGCAGTTTAT GACGATGGAC GGAACCTTTG 101 GTAACCCGGC CTCCCGTTCT CACCGTTTCG GCTGGCAGGC TGAAGAAGCG 151 GTAGATATCG CCCGTAATCA GATTGCCGAT CTGGTCGGCG CTGATCCGCG 201 TGAAATCGTC TTTACCTCTG GTGCAACCGA ATCTGACAAC CTGGCGATCA 251 AAGGTGCAGC CAACTTTTAT CAGAAAAAAG GCAAGCACAT CATCACCAGC 301 AAAACCGAAC ACAAAGCGGT ACTGGATACC TGCCGTCAGC TGGAGCGCGA 351 AGGTTTTGAA GTCACCTACC TGGCACCGCA GCGTAACGGC ATTATCGACC 401 TGAAAGAACT TGAAGCAGCG ATGCGTGACG ACACCATCCT CGTGTCCATC 451 ATGCACGTAA ATAACGAAAT CGGCGTGGTG CAGGATATCG CGGCTATCGG 501 CGAAATGTGC CGTGCTCGTG GCATTATCTA TCACGTTGAT GCAACCCAGA 551 GCGTGGGTAA ACTGCCTATC GACCTGAGCC AGTTGAAAGT TGACCTGATG 601 TCTTTCTCCG GTCACAAAAT CTATGGCCCG AAAGGTATCG GTGCGCTGTA 651 TGTACGTCGT AAACCGCGCG TACGCATCGA AGCGCAAATG CACGGCGGCG 701 GTCACGAGCG CGGTATGCGT TCCGGCACTC TGCCTGTTCA CCAGATCGTC 751 GGAATGGGCG AGGCCTATCG CATCGCAAAA GAAGAGATGGCGACCGAGAT 801 GGAACGTCTG CGCGGCCTGC GTAACCGTCT GTGGAACGGC ATCAAAGATA 851 TCGAAGAAGT TTACCTGAAC GGTGACCTGG AACACGGTGC GCCGAACATT 901 CTCAACGTCA GCTTCAACTA CGTTGAAGGT GAGTCGCTGA TTATGGCGCT 951 GAAAGACCTC GCAGTTTCTT CAGGTTCCGC CTGTACGTCA GCAAGCCTCG 1001 AACCGTCCTA CGTGCTGCGC GCGCTGGGGC TGAACGACGA GCTGGCACAT 1051 AGCTCTATCC GTTTCTCTTT AGGTCGTTTT ACTACTGAAG AAGAGATCGA 1101 CTACACCATC GAGTTAGTTC GTAAATCCAT CGGTCGTCTG CGTGACCTTT 62 FH12512877.6 Attorney Docket No.: NEX-16225 1151 CTCCGCTGTG GGAAATGTAC AAGCAGGGCG TGGATCTGAACAGCATCGAA 1201 TGGGCTCATC ATtaa (SEQ ID NO: 36) decR is a DNA-binding transcriptional activator, which contains a helix-turn-helix motif to bind DNA in its N-terminal domain. An example of decR is provided by the sequence of SEQ ID NO: 37, which is a DNA-binding transcriptional activator from Escherichia coli. Homologues of decR from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of decR in the instant invention are represented by UniProt entries: 0ACJ5, P0ACJ6, P0ACJ7, Q22230, Q23116, A0A812T6V2, A0A5E7FH89, A0A3G8JGB0, A0A451D390, A0A451DDE8, A0A517DXY7, A0A5B8R5Y8, A0A7D3P6R8, A0A7X1EFH1, A0A8E6NHW6, A0A8E9YAW5, A0A916I1J9, A0A916MYW8, A0A977N6I8, A0AA35XS47, and A0AAD2V8S9. An example of DNA-binding transcriptional activator is provided by the amino acid sequence of SEQ ID NO: 37, which is DNA-binding transcriptional activator from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 38. The UniProt entries listed herein are incorporated by reference in their entireties. decR (E. coli) 1 MLDKIDRKLL ALLQQDCTLS LQALAEAVNL TTTPCWKRLK RLEDDGILIG 51 KVALLDPEKI GLGLTAFVLI KTQHHSSEWY CRFVTVVTEM PEVLGFWRMA 101 GEYDYLMRVQ VADMKRYDEF YKRLVNSVPG LSDVTSSFAM EQIKYTTSLP 151 IE (SEQ ID NO: 37) decR (E. coli) 1 atgTTAGATA AAATTGACCG TAAGCTGCTG GCCTTACTGC AGCAGGATTG 51 CACCCTCTCT TTGCAGGCAC TGGCTGAAGC CGTTAATCTG ACAACCACCC 101 CTTGCTGGAA GCGCCTGAAA CGGCTGGAGG ACGACGGTAT CCTTATCGGC 151 AAAGTCGCCC TGCTGGATCC GGAAAAAATA GGCCTCGGCC TGACCGCTTT 201 TGTGCTGATA AAAAcGCAAC ATCACAGCAG CGAATGGTAT TGCCGCTTTG 251 TCACGGTGGT TACCGAAATG CCAGAAGTGC TGGGGTTCTG GCGCATGGCT 301 GGTGAATACG ATTATCTGAT GCGCGTCCAG GTTGCCGACA TGAAACGCTA 351 CGACGAGTTT TATAAGCGTC TGGTAAACAG CGTGCCGGGG CTGTCGGACG 401 TCACTTCCAG CTTCGCGATG GAACAGATTA AATACACCAC TTCTTTACCC 451 ATCGAAtaa (SEQ ID NO: 38) 63 FH12512877.6 Attorney Docket No.: NEX-16225 The UniProt entries listed herein are incorporated by reference in their entireties. The engineered microorganism may lack activity of these enzymes. The term “activity” refers to the total capacity of a cell to perform a function. For example, a genetic modification that decreases the activity of an enzyme in a cell may reduce the amount of the enzyme in a cell or reduce the efficiency of the enzyme. An enzyme knockout reduces the amount of the enzyme in the cell. Alternatively, a mutation to an enzyme gene may reduce the efficiency of its enzyme protein product with little effect on the amount of cellular enzyme. Mutations that reduce the efficiency of the enzyme may affect the active site, for example, by changing one or more active site residues; they may impair the enzyme’s kinetics, for example, by sterically blocking substrates or products; they may affect protein folding or dynamics, for example, by reducing the proportion of properly-folded enzymes; they may affect protein localization; or they may affect protein degradation, for example, by adding one or more protein cleavage sites or by adding one or more residues or amino acid sequences that target the protein for proteolysis. These mutations affect coding regions. Mutations that decrease the enzyme activity may instead affect the transcription or translation of the gene. For example, mutation to an enzyme enhancer or promoter can reduce the enzyme activity by reducing its expression. Mutating or deleting the non-coding portions of an enzyme gene, such as its introns, may also reduce transcription or translation. Additionally, mutations to the upstream regulators of an enzyme may its activity; for example, the over-expression of one or more repressors may decrease the enzyme activity, and a knockout or mutation of one or more activators may similarly decrease the enzyme activity. The enzymes may be knocked out in the engineered microorganism. The term “knockout mutation” or “knockout” refers to a genetic modification that prevents a native gene from being transcribed and translated into a functional protein. Different approaches may be used to knockout the enzyme gene (See, e.g., Dulermo et al., Biochimica Biophysica Acta 1831:1486 (2013)). The term “native” refers to the composition of a cell or parent cell prior to a transformation event. A “native gene” refers to a nucleotide sequence that encodes a protein that has not been introduced into a cell by a transformation event. A “native protein” refers to an amino acid sequence that is encoded by a native gene. Controlled Promoter In some embodiments, the engineered microorganism disclosed herein comprises at least one heterologous gene, which is operably linked to a promoter (e.g., an inducible 64 FH12512877.6 Attorney Docket No.: NEX-16225 promoter) that is activated or repressed by an environmental cue. In some embodiments, the environmental cue is H2S, reactive oxygen species (ROS), thiosulfate, or interleukins. In some embodiments, the promoter is a ROS-activated promoter such as the oxyR (transcription factor) and oxyS (promoter) gene-promoter from E. coli. The ROS activates the OxyR, which activates the OxyS promoter. OxyR is a transcription factor. An example of OxyR is provided by the sequence of SEQ ID NO: 39, which is OxyR from Escherichia coli. Homologues of OxyR from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of OxyR in the instant invention are represented by UniProt entries: P0ACQ4, P0ACQ5, P0ACQ6, L8EYU3, P71318, Q9X725, P52677, O87324, P52678, O87883, Q9X5P2, P44418, and Q9HTL4. An example of OxyR is provided by the amino acid sequence of SEQ ID NO: 39, which is OxyR from Escherichia coli and encoded by the nucleic acid sequence of SEQ ID NO: 40. The UniProt entries listed herein are incorporated by reference in their entireties. oxyR (E. coli) 1 MNIRDLEYLV ALAEHRHFRR AADSCHVSQP TLSGQIRKLE DELGVMLLER 51 TSRKVLFTQA GMLLVDQART VLREVKVLKE MASQQGETMS GPLHIGLIPT 101 VGPYLLPHII PMLHQTFPKL EMYLHEAQTH QLLAQLDSGK LDCVILALVK 151 ESEAFIEVPL FDEPMLLAIY EDHPWANREC VPMADLAGEK LLMLEDGHCL 201 RDQAMGFCFE AGADEDTHFR ATSLETLRNM VAAGSGITLL PALAVPPERK 251 RDGVVYLPCI KPEPRRTIGL VYRPGSPLRS RYEQLAEAIR ARMDGHFDKV 301 LKQAV (SEQ ID NO: 39) oxyR (E. coli) 1 atgaatattc gtgatcttga gtacctggtg gcattggctg aacaccgcca 51 ttttcggcgt gcggcagatt cctgccacgt tagccagccg acgcttagcg 101 ggcaaattcg taagctggaa gatgagctgg gcgtgatgtt gctggagcgg 151 accagccgta aagtgttgtt cacccaggcg ggaatgctgc tggtggatca 201 ggcgcgtacc gtgctgcgtg aggtgaaagt ccttaaagag atggcaagcc 251 agcagggcga gacgatgtcc ggaccgctgc acattggttt gattcccaca 301 gttggaccgt acctgctacc gcatattatc cctatgctgc accagacctt 351 tccaaagctg gaaatgtatc tgcatgaagc acagacccac cagttactgg 65 FH12512877.6 Attorney Docket No.: NEX-16225 401 cgcaactgga cagcggcaaa ctcgattgcg tgatcctcgc gctggtgaaa 451 gagagcgaag cattcattga agtgccgttg tttgatgagc caatgttgct 501 ggctatctat gaagatcacc cgtgggcgaa ccgcgaatgc gtaccgatgg 551 ccgatctggc aggggaaaaa ctgctgatgc tggaagatgg tcactgtttg 601 cgcgatcagg caatgggttt ctgttttgaa gccggggcgg atgaagatac 651 acacttccgc gcgaccagcc tggaaactct gcgcaacatg gtggcggcag 701 gtagcgggat cactttactg ccagcgctgg ctgtgccgcc ggagcgcaaa 751 cgcgatgggg ttgtttatct gccgtgcatt aagccggaac cacgccgcac 801 tattggcctg gtttatcgtc ctggctcacc gctgcgcagc cgctatgagc 851 agctggcaga ggccatccgc gcaagaatgg atggccattt cgataaagtt 901 ttaaaacagg cggtttaa (SEQ ID NO: 40) OxyS is a promoter. An example of OxyS is provided by the nucleic acid sequence of SEQ ID NO: 41, which is OxyS from Escherichia coli. Homologues of OxyS from microorganisms other than Escherichia coli can be used in the microorganisms and methods described herein. oxyS promoter (E. coli) 1 gaaACGGAGC GGCACCTCTT TTAACCCTTG AAGTCACTGC CCGTTTCGAG 51 AGTTTCTCAA CTCGAATAAC TAAAGCCAAC GTGAACTTTT GCGGATCTCC 101 AGGATCCGCT TTTTttt (SEQ ID NO: 41) In some embodiments, the promoter is a luminal H2S-activated promoter, such as an IR9 promoter from B. licheniformis. In some embodiments, the engineered microorganism expresses NreB and NreC. In some embodiments, the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter from B. licheniformis. nreB senses H2S and phosphorylates the NreC. An example of nreB is provided by the sequence of SEQ ID NO: 42, which is nreB from B. licheniformis. Homologues of nreB from microorganisms other than B. licheniformis can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of nreB in the instant invention are represented by UniProt entries: Q7WZY5, Q4L8Q7, Q5HDG4, Q2YZ41, Q6G6S9, Q5HLK5, Q7A028, Q6GE41, Q931F6, Q99RN7, A6QJN2, A8Z581, Q8CR97, A5IVH3, A6U4C1, Q2FVM6, Q2FEA5, A7X624, O28682, A0A1W7A8K1, A0A1X6ZAH4, and Q5WK46. 66 FH12512877.6 Attorney Docket No.: NEX-16225 An example of nreB is provided by the amino acid sequence of SEQ ID NO: 42, which is nreB from B. licheniformis and encoded by the nucleic acid sequence of SEQ ID NO: 43. The UniProt entries listed herein are incorporated by reference in their entireties. nreB (B. licheniformis) 1 MMCQNPARYT EEGMSNESGY LRQIFDHLQD GIIMMDQERT ILVINPSAEK 51 MTGWKLGDKV PYCSYCQTRK LEAGEERCYL LAKREIPYFL SSMPTYEGRF 101 VDMEMSTAVI SENGDQMEVL LVLKDLTMKK KEEEAKISKL VLQKTLEAQE 151 NEHKRLAQEL HDGVGQSLYS VSVGIQAIQS RMEQEETFKD YMQDIIDELE 201 KAIQDVKLYS LQLRPHSLDQ LGLIPAVKHL VSSLNKTHQD VSITFASSDI 251 SNRLLPIFEI NLYRIIQEAL HNALKYSQAT LIEVILYKED GELVLIIQDD 301 GIGFERGLTE EGLGFKHMKE RVDQMDGSLR IHSALQSGTT IKVKVQDKEG 351 KESDQGIAGR (SEQ ID NO: 42) nreB (B. licheniformis) 1 ATGATGTGTC AAAACCCGGC TCGGTATACA GAAGAAGGAA TGTCAAATGA 51 AAGCGGCTAT TTAAGGCAGA TCTTCGACCA TTTGCAGGAT GGGATCATCA 101 TGATGGATCA GGAACGCACA ATTCTGGTGA TTAATCCGTC CGCAGAGAAG 151 ATGACGGGAT GGAAACTAGG GGATAAGGTT CCGTACTGTT CCTACTGCCA 201 AACGAGAAAA CTGGAAGCGG GAGAAGAGCG TTGTTATTTG CTGGCCAAGC 251 GGGAAATTCC TTATTTTCTC TCCTCGATGC CCACCTATGA AGGGCGATTC 301 GTCGACATGG AGATGAGTAC GGCTGTCATT TCCGAAAACG GCGATCAAAT 351 GGAAGTTCTT TTGGTCCTGA AAGATTTAAC AATGAAGAAA AAGGAGGAAG 401 AAGCGAAGAT CTCCAAGCTG GTTCTGCAAA AAACGTTAGA GGCCCAGGAA 451 AACGAACACA AGCGGCTTGC CCAGGAACTG CACGATGGTG TAGGGCAATC 501 GCTTTATTCG GTTTCAGTAG GCATTCAAGC GATTCAATCG CGCATGGAGC 551 AGGAAGAAAC ATTTAAAGAT TACATGCAGG ACATCATCGA TGAACTGGAA 601 AAAGCAATCC AAGACGTCAA GCTCTACTCT CTCCAGCTGC GCCCGCACAG 651 TCTCGATCAA TTGGGGCTGA TCCCTGCTGT CAAGCATCTT GTTTCCAGCT 701 TAAACAAGAC GCATCAGGAT GTTTCTATTA CGTTTGCCTC AAGCGATATC 751 AGCAATCGCT TGCTGCCGAT TTTTGAAATC AATTTGTACC GCATCATTCA 801 GGAGGCGCTT CATAATGCCC TGAAATATTC GCAGGCGACA CTTATTGAAG 851 TCATACTTTA CAAAGAAGAC GGCGAGCTCG TTTTGATCAT TCAGGACGAT 901 GGCATTGGTT TTGAACGCGG GCTGACAGAG GAAGGCCTGG GGTTCAAACA 67 FH12512877.6 Attorney Docket No.: NEX-16225 951 TATGAAAGAG AGAGTCGATC AGATGGATGG AAGTCTTCGA ATTCACTCTG 1001 CACTTCAGAG TGGCACGACGATTAAAGTGAAAGTACAGGACAAGGAGGGG 1051 AAGGAGAGTG ATCAGGGTAT TGCTGGTCGA TGA (SEQ ID NO: 43) nreC activates the IR9 promoter after being phosphorylated by the NreC. An example of nreC is provided by the sequence of SEQ ID NO: 44, which is nreC from B. licheniformis. Homologues of nreC from microorganisms other than B. licheniformis can be used in the microorganisms and methods described herein. Non-limiting examples of the homologs of nreC in the instant invention are represented by UniProt entries: A0A6C1WYL6, A0A0N8NSV0, A0A173RH09, A0A1C5NKX9, A0A1V4VQ91, A0A2T0B1Q3, A0A9P1PB99, A0A174ZPY8, A0A1C5W555, A0A1C6HPN6, A0A1J5NKL0, A0A2U3KWW9, A0A6F8ZHG4, A0A162MZH6, A0A1V4W492, A0A1V5BU73, A0A2T0BMN6, A0A0L6Z5H0, A0A173XW97, A0A174CUN1, A0A174ICM1, and A0A174Q4V9. An example of nreC is provided by the amino acid sequence of SEQ ID NO: 44, which is nreC from B. licheniformis and encoded by the nucleic acid sequence of SEQ ID NO: 45. The UniProt entries listed herein are incorporated by reference in their entireties. nreC (B. licheniformis) 1 VIRVLLVDDH MMIRKGIRVL LEGFSGIEIA GESNNGNEAV LSAGQLKPDV 51 VLMDLSMPNG LDGFTASSEI RKLNPSVKIV ILTMHDEEIF VQKAIEAGAH 101 GYVLKNSHYR LLYQAIVEVY RSNLFYKTSV SQDIIDQWLN SEPKKPTSVL 151 TVREKEILRF IVLGYANKEI ADKLSISVKT VENHKTNMMQ KLDLDSKHEL 201 IQYAIKNKYL DLSL (SEQ ID NO: 44) nreC (B. licheniformis) 1 GTGATCAGGG TATTGCTGGT CGATGACCAT ATGATGATTC GCAAGGGCAT 51 CCGTGTCCTT TTGGAAGGCT TTTCTGGAAT TGAAATTGCG GGAGAAAGCA 101 ATAATGGCAA CGAAGCCGTT CTTAGCGCCG GACAGTTAAA GCCGGATGTC 151 GTGCTGATGG ATTTGTCGAT GCCGAACGGG TTGGACGGAT TCACAGCGAG 201 CAGTGAGATC CGAAAGTTGA ATCCTTCTGT TAAAATCGTG ATTTTGACAA 251 TGCATGATGA GGAAATTTTT GTCCAAAAAG CAATAGAGGC GGGGGCGCAT 301 GGCTACGTCT TGAAAAACAG CCATTATCGG TTGCTTTATC AGGCGATTGT 351 CGAAGTGTAC AGGAGCAATC TCTTTTACAA AACATCTGTA TCGCAAGACA 68 FH12512877.6 Attorney Docket No.: NEX-16225 401 TCATTGATCA ATGGCTCAAT TCAGAGCCCA AAAAGCCGAC CTCTGTATTA 451 ACTGTCCGCG AAAAGGAGAT TCTCAGATTC ATTGTGCTGG GTTATGCCAA 501 TAAGGAGATT GCCGATAAAC TCTCAATCAG CGTCAAAACC GTCGAAAACC 551 ACAAAACGAA TATGATGCAG AAGTTAGATC TGGACTCGAA ACACGAATTG 601 ATTCAATATG CGATCAAAAA TAAATATCTC GATCTGTCGT TGTAA (SEQ ID NO: 45) IR-9 is a promoter. An example of IR-9 is provided by the nucleic acid sequence of SEQ ID NO: 46, which is IR-9 from B. licheniformis. Homologues of IR-9 from microorganisms other than B. licheniformis can be used in the microorganisms and methods described herein. IR-9 promoter (B. licheniformis) 1 Catacggccc cttaacccct gtcagcttgt gaagacggag ctcacataaa 51 agtaggggag ttcccctata cagaaaaagg aagattgatg ttaacttaaa 101 aaaagagaga cgcatcatta agaaaaacag cagctttcta taaacataag 151 ggggttgacc (SEQ ID NO: 46) In some embodiments, the promoter is a thiosulfate-activated promoter. The thiosulfate-activated promoter may be a phsA342 promoter from S. halifaxensis. In some embodiments, the engineered microorganism expresses a thiosulfate sensor (e.g., thsS), which activates a transcription factor (e.g., thsR). The thsS is a membrane-bound thiosulfate sensor which phosphorylates the transcription factor, thsR, which binds to the phsA342 promoter to drive gene expression from Shewanella halifaxensis. In some embodiments, the engineered microorganism expresses a transcription factor that is activated by thiosulfate. In some embodiments, the activated transcription factor activates the promoter. thsS is a membrane-bound thiosulfate sensor which phosphorylates the transcription factor, thsR. An example of thsS is provided by the sequence of SEQ ID NO: 47, which is thsS from Shewanella halifaxensis. Homologues of thsS from microorganisms other than Shewanella halifaxensis can be used in the microorganisms and methods described herein. An example of thsS is provided by the amino acid sequence of SEQ ID NO: 47, which is thsS from Shewanella halifaxensis and encoded by the nucleic acid sequence of SEQ ID NO: 48. 69 FH12512877.6 Attorney Docket No.: NEX-16225 thsS (Shewanella halifaxensis) 1 MSRLLLCICV LLFSSVAWSK PQQFYVGVLA NWGHQQAVER WTPMMEYLNE 51 HVPDAEFHVY PGNFKALNLA MELGQIQFII TNPGQYLYLS NQYPLSWLAT 101 MRSKRHDGTT SAIGSAIIVR ADSDYRTLYD LKGKVVAASD PHALGGYQAT 151 VGLMHSLGMD PDTFFGETKF LGFPLDPLLY QVRDGNVDAA ITPLCTLEDM 201 VARGVLKSSD FRVLNPSRPD GVECQCSTTL YPNWSFAATE SVSTELSKEI 251 TQALLELPSD SPAAIKAQLT GWTSPISQLA VIKLFKELHV KTPDSSRWEA 301 VKKWLEENRH WGILSVLVFI IATLYHLWIE YRFHQKSSSL IESERQLKQQ 351 AVALERLQSA SIVGEIGAGL AHEINQPIAA ITSYSEGGIM RLQGKEQADT 401 DSCIELLEKI HKQSTRAGEV VHRIRGLLKR REAVMVDVNI LTLVEESISL 451 LRLELARREI QINTQIKGEP FFITADRVGL LQVLINLIKN SLDAIAESDN 501 ARSGKINIEL DFKEYQVNVS IIDNGPGLAM DSDTLMATFY TTKMDGLGLG 551 LAICREVISN HDGHFLLSNR DDGVLGCVAT LNLKKRGSEV PIEV (SEQ ID NO: 47) nreB (Shewanella halifaxensis, codon optimized for E. coli) 1 atgtcccgcc tgctgctgtg tatctgtgtt ctgctgttct cttctgtggc 51 gtggtctaaa ccgcagcagt tttatgtggg cgtactggct aactggggtc 101 atcagcaagc cgttgaacgt tggaccccga tgatggagta tctgaacgaa 151 catgtgccgg acgcggaatt tcacgtctac ccgggcaact tcaaagcact 201 gaacctggca atggaactgg gccagattca gttcattatc actaacccgg 251 gccaatatct gtacctgagc aatcagtacc cgctgtcttg gctggcgacc 301 atgcgttcta agcgtcacga tggtaccact tctgcgatcg gttccgccat 351 tattgtccgc gcggacagcg actaccgcac cctgtacgac ctgaaaggta 401 aagtggtggc tgcgtccgac ccgcatgctc tgggtggcta ccaagcgacc 451 gtcggtctga tgcattccct gggcatggat ccggacacct tcttcggtga 501 aaccaagttt ctgggctttc cactggatcc gctgctgtac caagttcgtg 551 atggcaacgt tgacgcggcc attaccccac tgtgcactct ggaggacatg 601 gttgcacgcg gcgtactgaa atcttccgat tttcgtgtgc tgaaccctag 651 ccgcccggat ggtgtagaat gccagtgctc taccaccctg tacccgaact 701 ggtctttcgc tgcgactgag tctgtatcca ccgaactgtc taaagaaatc 751 acgcaggcac tgctggaact gccatccgac agcccggcag ctatcaaagc 801 gcaactgacc ggctggacca gcccgatctc ccaactggcg gtaatcaaac 851 tgttcaaaga gctgcacgta aaaaccccgg actctagccg ttgggaagcc 901 gttaagaagt ggctggaaga aaaccgtcac tggggtatcc tgtctgttct 70 FH12512877.6 Attorney Docket No.: NEX-16225 951 ggtgttcatc attgcaacgc tgtatcacct gtggattgaa taccgcttcc 1001 accaaaaaag ctcttctctg atcgaatctg aacgtcagct gaaacagcaa 1051 gctgttgccc tggaacgtct gcaatctgct agcatcgttg gtgaaattgg 1101 tgcgggtctg gcccacgaga ttaatcagcc gatcgctgca attacctctt 1151 attctgaagg tggcatcatg cgcctgcaag gtaaagaaca ggcggatacg 1201 gatagctgca tcgaactgct ggaaaaaatc cacaaacaga gcactcgcgc 1251 aggcgaagtg gtgcaccgca tccgtggtct gctgaaacgt cgtgaagcgg 1301 tgatggtaga tgttaacatc ctgaccctgg tggaagaatc catcagcctg 1351 ctgcgtctgg agctggcacg tcgcgaaatc cagatcaaca ctcagatcaa 1401 aggtgaaccg ttcttcatta ctgccgaccg cgttggcctg ctgcaagttc 1451 tgattaacct gatcaaaaac tccctggacg cgatcgctga atctgataat 1501 gcccgttctg gtaaaatcaa catcgaactg gactttaaag agtaccaggt 1551 aaacgtctcc atcatcgata acggtccggg cctggcgatg gattctgaca 1601 ctctgatggc tacgttttac actaccaaaa tggatggcct gggcctgggt 1651 ctggcaatct gccgcgaagt tatcagcaac cacgacggcc acttcctgct 1701 gtccaaccgt gacgacggcg ttctgggctg tgtggcaacc ctgaatctga 1751 aaaaacgcgg ttctgaagtg ccgatcgaag tctaataa (SEQ ID NO: 48) thsR is a transcription factor, which is phosphorylated by thsS and binds to the phsA342 promoter to drive gene expression An example of thsR is provided by the sequence of SEQ ID NO: 49, which is thsR from Shewanella halifaxensis. Homologues of thsR from microorganisms other than Shewanella halifaxensis can be used in the microorganisms and methods described herein. An example of thsR is provided by the amino acid sequence of SEQ ID NO: 49, which is thsR from Shewanella halifaxensis and encoded by the nucleic acid sequence of SEQ ID NO: 50. thsR (Shewanella halifaxensis) 1 MQQQINGPVY LVDDDEAIID SIDFLMEGYG YKLNSFNCGD RFLAEVDLTQ 51 AGCVILDARM PGLTGPQVQQ LLSDAKSPLA VIFLTGHGDV PMAVDAFKNG 101 AFDFFQKPVP GSLLSQSIAK GLTYSIDQHL KRTNQALIDT LSEREAQIFQ 151 LVIAGNTNKQ MANELCVAIR TIEVHRSKLM TKLGVNNLAE LVKLAPLLAH 201 KSE (SEQ ID NO: 49) 71 FH12512877.6 Attorney Docket No.: NEX-16225 thsR (Shewanella halifaxensis, codon optimized for E. coli) 1 atgcagcagc aaatcaacgg cccggtctac ctggtggatg atgatgaagc 51 cattatcgac tccatcgatt ttttgatgga gggctacggt tacaaactga 101 actcgtttaa ctgcggcgat cgctttttgg cagaagtcga tctcacccag 151 gcaggatgtg taattctgga tgcgcgtatg ccaggcttaa ctggtcctca 201 ggtgcaacag ctgctgagcg acgcgaaaag cccgcttgcg gtcatcttcc 251 tgaccggcca tggcgatgtt ccgatggcgg ttgatgcgtt caaaaatggc 301 gcgttcgatt tctttcaaaa acctgtgccg ggtagcttgc tcagtcagtc 351 aattgccaaa ggcttgactt attcaatcga tcaacatctg aaacgtacta 401 accaagcgtt aatcgacacg ctctcggaac gcgaagctca aatttttcaa 451 ctggtgattg caggcaacac caacaaacag atggctaacg agctttgcgt 501 ggctattcgt accattgagg ttcaccgtag caaactgatg accaaactgg 551 gtgttaacaa cctggctgaa ctggttaaac tggcgccgct gctggcacat 601 aaatccgaa (SEQ ID NO: 50) phsA342 is a promoter. An example of phsA342 is provided by the nucleic acid sequence of SEQ ID NO: 51, which is phsA342 from Shewanella halifaxensis. Homologues of phsA342 from microorganisms other than Shewanella halifaxensis can be used in the microorganisms and methods described herein. phsA342 promoter (Shewanella halifaxensis) 1 ttcaagcatt attatgctgt tttttgaagt gaatgtgcgg ccatctagcc 51 gcacattttg catctaaaac atgcagtcat cagcaaaata ataaactttt 101 ccccaatatg tggtttacca caatttacag gaattcactc ctgtggtggt 151 gcaaatttga actgtgaatt gcttcacaaa cgccgctatc gcaatgtcag 201 tatgtggttt accacaatat ctaatatcac tctgctcaat aacaatgatg 251 aaaaccttag gaagaagtta attgtgttaa acagttaact aggggcttta 301 tctaacgctc tcctaaggac aactgtcatt gggagattta ac (SEQ ID NO: 51) In some embodiments, the promoter is an interleukin-responsive or pro-inflammatory- responsive promoter. The Interleukin (IL) may be IL-1, IL-4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 and pro- inflammatory may be tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein 72 FH12512877.6 Attorney Docket No.: NEX-16225 (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, and 28, and the C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, and CX3CL1. For example, the Nuclear factor-κB (NF-κB) transcription factors (p65 (RelA), RelB, c-Rel, p105p50 (NF-κB1), and p100 / 52 (NF-κB2)) respond to IL-1 and tumor necrosis factor (TNF) and bind to the consensus sequence 5’-GGGRNYYCC-3’ (SEQ ID NO: 52) where R = A or G; N = A, C, G, or T; W = A or T; and Y = C or T. The NF- κB transcription factors regulate hundreds of genes. The consensus binding sequence can be used to bind activated NF-κB transcription factors to drive expression of H2S consumption or production pathways in microbes. Physiologically, interleukins and chemokines produced by the human immune system leads to biological cascades and subsequent changes in gene expression. These biological cascades can be adapted to our engineered bacteria to turn on the H2S production or consumption pathways. In some embodiments, the engineered microorganism expresses a transcription factor that is activated by an interleukin or pro-inflammatory cytokine or chemokine. In some embodiments, the activated transcription factor activates the promoter. "Inducible promoter" is a promoter that mediates the transcription of an operably linked gene in response to a particular stimulus. "In operable linkage" refers to a functional linkage between two nucleic acid sequences, such a control sequence (typically a promoter) and the linked sequence (typically a sequence that encodes a protein, also called a coding sequence). A promoter is in operable linkage with a gene if it can mediate transcription of the gene. A "promoter" is a nucleic acid control sequence that directs the transcription of a nucleic acid. As used herein, a promoter includes the necessary nucleic acid sequences near the start site of transcription. A promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. Microorganisms In some embodiments, the engineered microorganism is bacterium such as Turicibacter sanguinis, Escherichia coli, or Bacteroides thetaiotaomicron. In some embodiments, the engineered microorganism is Abiotrophia defectiva, Abiotrophia para_adiacens, Abiotrophia sp. oral clone P4PA_155 P1, Acetanaerobacterium 73 FH12512877.6 Attorney Docket No.: NEX-16225 elongatum, Acetivibrio cellulolyticus, Acetivibrio ethanolgignens, Acetobacter aceti, Acetobacter fabarum, Acetobacter lovaniensis, Acetobacter malorum, Acetobacter orientalis, Acetobacter pasteurianus, Acetobacter pomorum, Acetobacter syzygii, Acetobacter tropicalis, Acetobacteraceae bacterium AT_5844, Acholeplasma laidlawii, Achromobacter denitrificans, Achromobacter piechaudii, Achromobacter xylosoxidans, Acidaminococcus fermentans, Acidaminococcus intestini, Acidaminococcus sp. D21, Acidilobus saccharovorans, Acidithiobacillus ferrivorans, Acidovorax sp.98_63833, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter genomosp. C1, Acinetobacter haemolyticus, Acinetobacter johnsonii, Acinetobacter junii, Acinetobacter lwoffii, Acinetobacter parvus, Acinetobacter radioresistens, Acinetobacter schindleri, Acinetobacter sp.56A1, Acinetobacter sp. CIP 101934, Acinetobacter sp. CIP 102143, Acinetobacter sp. CIP 53.82, Acinetobacter sp. M16_22, Acinetobacter sp. RUH2624, Acinetobacter sp. SH024, Actinobacillus actinomycetemcomitans, Actinobacillus minor, Actinobacillus pleuropneumoniae, Actinobacillus succinogenes, Actinobacillus ureae, Actinobaculum massiliae, Actinobaculum schaalii, Actinobaculum sp. BM#101342, Actinobaculum sp. P2P_19 P1, Actinomyces cardiffensis, Actinomyces europaeus, Actinomyces funkei, Actinomyces genomosp. C1, Actinomyces genomosp. C2, Actinomyces genomosp. P1 oral clone MB6_C03, Actinomyces georgiae, Actinomyces israelii, Actinomyces massiliensis, Actinomyces meyeri, Actinomyces naeslundii, Actinomyces nasicola, Actinomyces neuii, Actinomyces odontolyticus, Actinomyces oricola, Actinomyces orihominis, Actinomyces oris, Actinomyces sp.7400942, Actinomyces sp. c109, Actinomyces sp. CCUG 37290, Actinomyces sp. ChDC B197, Actinomyces sp. GEJ15, Actinomyces sp. HKU31, Actinomyces sp. ICM34, Actinomyces sp. ICM41, Actinomyces sp. ICM47, Actinomyces sp. ICM54, Actinomyces sp. M2231_94_1, Actinomyces sp. oral clone GU009, Actinomyces sp. oral clone GU067, Actinomyces sp. oral clone IO076, Actinomyces sp. oral clone IO077, Actinomyces sp. oral clone IP073, Actinomyces sp. oral clone IP081, Actinomyces sp. oral clone JA063, Actinomyces sp. oral taxon 170, Actinomyces sp. oral taxon 171, Actinomyces sp. oral taxon 178, Actinomyces sp. oral taxon 180, Actinomyces sp. oral taxon 848, Actinomyces sp. oral taxon C55, Actinomyces sp. TeJ5, Actinomyces urogenitalis, Actinomyces viscosus, Adlercreutzia equolifaciens, Aerococcus sanguinicola, Aerococcus urinae, Aerococcus urinaeequi, Aerococcus viridans, Aeromicrobium marinum, Aeromicrobium sp. JC14, Aeromonas allosaccharophila, Aeromonas enteropelogenes, Aeromonas hydrophila, Aeromonas jandaei, Aeromonas salmonicida, Aeromonas trota, Aeromonas veronii, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella 74 FH12512877.6 Attorney Docket No.: NEX-16225 corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, Afipia genomosp.4, Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, Aggregatibacter segnis, Agrobacterium radiobacter, Agrobacterium tumefaciens, Agrococcus jenensis, Akkermansia muciniphila, Alcaligenes faecalis, Alcaligenes sp. CO14, Alcaligenes sp. S3, Alicyclobacillus acidocaldarius, Alicyclobacillus acidoterrestris, Alicyclobacillus contaminans, Alicyclobacillus cycloheptanicus, Alicyclobacillus herbarius, Alicyclobacillus pomorum, Alicyclobacillus sp. CCUG 53762, Alistipes finegoldii, Alistipes indistinctus, Alistipes onderdonkii, Alistipes putredinis, Alistipes shahii, Alistipes sp. HGB5, Alistipes sp. JC50, Alistipes sp. RMA 9912, Alkaliphilus metalliredigenes, Alkaliphilus oremlandii, Alloscardovia omnicolens, Alloscardovia sp. OB7196, Anaerobaculum hydrogeniformans, Anaerobiospirillum succiniciproducens, Anaerobiospirillum thomasii, Anaerococcus hydrogenalis, Anaerococcus lactolyticus, Anaerococcus octavius, Anaerococcus prevotii, Anaerococcus sp.8404299, Anaerococcus sp.8405254, Anaerococcus sp.9401487, Anaerococcus sp.9403502, Anaerococcus sp. gpac104, Anaerococcus sp. gpac126, Anaerococcus sp. gpac155, Anaerococcus sp. gpac199, Anaerococcus sp. gpac215, Anaerococcus tetradius, Anaerococcus vaginalis, Anaerofustis stercorihominis, Anaeroglobus geminatus, Anaerosporobacter mobilis, Anaerostipes caccae, Anaerostipes sp.3_2_56FAA, Anaerotruncus colihominis, Anaplasma marginale, Anaplasma phagocytophilum, Aneurinibacillus aneurinilyticus, Aneurinibacillus danicus, Aneurinibacillus migulanus, Aneurinibacillus terranovensis, Aneurinibacillus thermoaerophilus, Anoxybacillus contaminans, Anoxybacillus flavithermus, Arcanobacterium haemolyticum, Arcanobacterium pyogenes, Arcobacter butzleri, Arcobacter cryaerophilus, Arthrobacter agilis, Arthrobacter arilaitensis, Arthrobacter bergerei, Arthrobacter globiformis, Arthrobacter nicotianae, Atopobium minutum, Atopobium parvulum, Atopobium rimae, Atopobium sp. BS2, Atopobium sp. F0209, Atopobium sp. ICM42b10, Atopobium sp. ICM57, Atopobium vaginae, Aurantimonas coralicida, Aureimonas altamirensis, Auritibacter ignavus, Averyella dalhousiensis, Bacillus aeolius, Bacillus aerophilus, Bacillus aestuarii, Bacillus alcalophilus, Bacillus amyloliquefaciens, Bacillus anthracis, Bacillus atrophaeus, Bacillus badius, Bacillus cereus, Bacillus circulans, Bacillus clausii, Bacillus coagulans, Bacillus firmus, Bacillus flexus, Bacillus fordii, Bacillus gelatini, Bacillus halmapalus, Bacillus halodurans, Bacillus 75 FH12512877.6 Attorney Docket No.: NEX-16225 herbersteinensis, Bacillus horti, Bacillus idriensis, Bacillus lentus, Bacillus licheniformis, Bacillus megaterium, Bacillus nealsonii, Bacillus niabensis, Bacillus niacini, Bacillus pocheonensis, Bacillus pumilus, Bacillus safensis, Bacillus simplex, Bacillus sonorensis, Bacillus sp.10403023 MM10403188, Bacillus sp.2_A_57_CT2, Bacillus sp.2008724126, Bacillus sp.2008724139, Bacillus sp.7_16AIA, Bacillus sp.9_3AIA, Bacillus sp. AP8, Bacillus sp. B27(2008), Bacillus sp. BT1B_CT2, Bacillus sp. GB1.1, Bacillus sp. GB9, Bacillus sp. HU19.1, Bacillus sp. HU29, Bacillus sp. HU33.1, Bacillus sp. JC6, Bacillus sp. oral taxon F26, Bacillus sp. oral taxon F28, Bacillus sp. oral taxon F79, Bacillus sp. SRC_DSF1, Bacillus sp. SRC_DSF10, Bacillus sp. SRC_DSF2, Bacillus sp. SRC_DSF6, Bacillus sp. tc09, Bacillus sp. zh168, Bacillus sphaericus, Bacillus sporothermodurans, Bacillus subtilis, Bacillus thermoamylovorans, Bacillus thuringiensis, Bacillus weihenstephanensis, Bacteroidales bacterium ph8, Bacteroidales genomosp. P1, Bacteroidales genomosp. P2 oral clone MB1_G13, Bacteroidales genomosp. P3 oral clone MB1_G34, Bacteroidales genomosp. P4 oral clone MB2_G17, Bacteroidales genomosp. P5 oral clone MB2_P04, Bacteroidales genomosp. P6 oral clone MB3_C19, Bacteroidales genomosp. P7 oral clone MB3_P19, Bacteroidales genomosp. P8 oral clone MB4_G15, Bacteroides acidifaciens, Bacteroides barnesiae, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides clarus, Bacteroides coagulans, Bacteroides coprocola, Bacteroides coprophilus, Bacteroides dorei, Bacteroides eggerthii, Bacteroides faecis, Bacteroides finegoldii, Bacteroides fluxus, Bacteroides fragilis, Bacteroides galacturonicus, Bacteroides helcogenes, Bacteroides heparinolyticus, Bacteroides intestinalis, Bacteroides massiliensis, Bacteroides nordii, Bacteroides oleiciplenus, Bacteroides ovatus, Bacteroides pectinophilus, Bacteroides plebeius, Bacteroides pyogenes, Bacteroides salanitronis, Bacteroides salyersiae, Bacteroides sp.1_1_14, Bacteroides sp.1_1_30, Bacteroides sp. 1_1_6, Bacteroides sp.2_1_22, Bacteroides sp.2_1_56FAA, Bacteroides sp.2_2_4, Bacteroides sp.20_3, Bacteroides sp.3_1_19, Bacteroides sp.3_1_23, Bacteroides sp. 3_1_33FAA, Bacteroides sp.3_1_40A, Bacteroides sp.3_2_5, Bacteroides sp.315_5, Bacteroides sp.31SF15, Bacteroides sp.31SF18, Bacteroides sp.35AE31, Bacteroides sp. 35AE37, Bacteroides sp.35BE34, Bacteroides sp.35BE35, Bacteroides sp.4_1_36, Bacteroides sp.4_3_47FAA, Bacteroides sp.9_1_42FAA, Bacteroides sp. AR20, Bacteroides sp. AR29, Bacteroides sp. B2, Bacteroides sp. D1, Bacteroides sp. D2, Bacteroides sp. D20, Bacteroides sp. D22, Bacteroides sp. F_4, Bacteroides sp. NB_8, Bacteroides sp. WH2, Bacteroides sp. XB12B, Bacteroides sp. XB44A, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, 76 FH12512877.6 Attorney Docket No.: NEX-16225 Bacteroides xylanisolvens, Bacteroidetes bacterium oral taxon D27, Bacteroidetes bacterium oral taxon F31, Bacteroidetes bacterium oral taxon F44, Barnesiella intestinihominis, Barnesiella viscericola, Bartonella bacilliformis, Bartonella grahamii, Bartonella henselae, Bartonella quintana, Bartonella tamiae, Bartonella washoensis, Bdellovibrio sp. MPA, Bifidobacteriaceae genomosp. C1, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium gallicum, Bifidobacterium infantis, Bifidobacterium kashiwanohense, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium pseudolongum, Bifidobacterium scardovii, Bifidobacterium sp. HM2, Bifidobacterium sp. HMLN12, Bifidobacterium sp. M45, Bifidobacterium sp. MSX5B, Bifidobacterium sp. TM_7, Bifidobacterium thermophilum, Bifidobacterium urinalis, Bilophila wadsworthia, Bisgaard Taxon, Bisgaard Taxon, Bisgaard Taxon, Bisgaard Taxon, Blastomonas natatoria, Blautia coccoides, Blautia glucerasea, Blautia glucerasei, Blautia hansenii, Blautia hydrogenotrophica, Blautia luti, Blautia producta, Blautia schinkii, Blautia sp. M25, Blautia stercoris, Blautia wexlerae, Bordetella bronchiseptica, Bordetella holmesii, Bordetella parapertussis, Bordetella pertussis, Borrelia afzelii, Borrelia burgdorferi, Borrelia crocidurae, Borrelia duttonii, Borrelia garinii, Borrelia hermsii, Borrelia hispanica, Borrelia persica, Borrelia recurrentis, Borrelia sp. NE49, Borrelia spielmanii, Borrelia turicatae, Borrelia valaisiana, Brachybacterium alimentarium, Brachybacterium conglomeratum, Brachybacterium tyrofermentans, Brachyspira aalborgi, Brachyspira pilosicoli, Brachyspira sp. HIS3, Brachyspira sp. HIS4, Brachyspira sp. HIS5, Brevibacillus agri, Brevibacillus brevis, Brevibacillus centrosporus, Brevibacillus choshinensis, Brevibacillus invocatus, Brevibacillus laterosporus, Brevibacillus parabrevis, Brevibacillus reuszeri, Brevibacillus sp. phR, Brevibacillus thermoruber, Brevibacterium aurantiacum, Brevibacterium casei, Brevibacterium epidermidis, Brevibacterium frigoritolerans, Brevibacterium linens, Brevibacterium mcbrellneri, Brevibacterium paucivorans, Brevibacterium sanguinis, Brevibacterium sp. H15, Brevibacterium sp. JC43, Brevundimonas subvibrioides, Brucella abortus, Brucella canis, Brucella ceti, Brucella melitensis, Brucella microti, Brucella ovis, Brucella sp.83_13, Brucella sp. BO1, Brucella suis, Bryantella formatexigens, Buchnera aphidicola, Bulleidia extructa, Burkholderia ambifaria, Burkholderia cenocepacia, Burkholderia cepacia, Burkholderia mallei, Burkholderia multivorans, Burkholderia oklahomensis, Burkholderia pseudomallei, Burkholderia rhizoxinica, Burkholderia sp.383, Burkholderia xenovorans, Burkholderiales bacterium 1_1_47, Butyricicoccus pullicaecorum, Butyricimonas virosa, 77 FH12512877.6 Attorney Docket No.: NEX-16225 Butyrivibrio crossotus, Butyrivibrio fibrisolvens, Caldimonas manganoxidans, Caminicella sporogenes, Campylobacter coli, Campylobacter concisus, Campylobacter curvus, Campylobacter fetus, Campylobacter gracilis, Campylobacter hominis, Campylobacter jejuni, Campylobacter lari, Campylobacter rectus, Campylobacter showae, Campylobacter sp. FOBRC14, Campylobacter sp. FOBRC15, Campylobacter sp. oral clone BB120, Campylobacter sputorum, Campylobacter upsaliensis, Candidatus Arthromitus sp. SFB_mouse_Yit, Candidatus Sulcia muelleri, Capnocytophaga canimorsus, Capnocytophaga genomosp. C1, Capnocytophaga gingivalis, Capnocytophaga granulosa, Capnocytophaga ochracea, Capnocytophaga sp. GEJ8, Capnocytophaga sp. oral clone AH015, Capnocytophaga sp. oral clone ASCH05, Capnocytophaga sp. oral clone ID062, Capnocytophaga sp. oral strain A47ROY, Capnocytophaga sp. oral strain S3, Capnocytophaga sp. oral taxon 338, Capnocytophaga sp. S1b, Capnocytophaga sputigena, Cardiobacterium hominis, Cardiobacterium valvarum, Carnobacterium divergens, Carnobacterium maltaromaticum, Catabacter hongkongensis, Catenibacterium mitsuokai, Catonella genomosp. P1 oral clone MB5_P12, Catonella morbi, Catonella sp. oral clone FL037, Cedecea davisae, Cellulosimicrobium funkei, Cetobacterium somerae, Chlamydia muridarum, Chlamydia psittaci, Chlamydia trachomatis, Chlamydiales bacterium NS11, Chlamydiales bacterium NS13, Chlamydiales bacterium NS16, Chlamydophila pecorum, Chlamydophila pneumoniae, Chlamydophila psittaci, Chloroflexi genomosp. P1, Christensenella minuta, Chromobacterium violaceum, Chryseobacterium anthropi, Chryseobacterium gleum, Chryseobacterium hominis, Citrobacter amalonaticus, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter gillenii, Citrobacter koseri, Citrobacter murliniae, Citrobacter rodentium, Citrobacter sedlakii, Citrobacter sp.30_2, Citrobacter sp. KMSI_3, Citrobacter werkmanii, Citrobacter youngae, Cloacibacillus evryensis, Clostridiaceae bacterium END_2, Clostridiaceae bacterium JC13, Clostridiales bacterium 1_7_47FAA, Clostridiales bacterium 9400853, Clostridiales bacterium 9403326, Clostridiales bacterium oral clone P4PA_66 P1, Clostridiales bacterium oral taxon 093, Clostridiales bacterium oral taxon F32, Clostridiales bacterium ph2, Clostridiales bacterium SY8519, Clostridiales genomosp. BVAB3, Clostridiales sp. SM4_1, Clostridiales sp. SS3_4, Clostridiales sp. SSC_2, Clostridium acetobutylicum, Clostridium aerotolerans, Clostridium aldenense, Clostridium aldrichii, Clostridium algidicarnis, Clostridium algidixylanolyticum, Clostridium aminovalericum, Clostridium amygdalinum, Clostridium argentinense, Clostridium asparagiforme, Clostridium baratii, Clostridium bartlettii, Clostridium beijerinckii, Clostridium bifermentans, Clostridium bolteae, Clostridium botulinum, 78 FH12512877.6 Attorney Docket No.: NEX-16225 Clostridium butyricum, Clostridium cadaveris, Clostridium carboxidivorans, Clostridium carnis, Clostridium celatum, Clostridium celerecrescens, Clostridium cellulosi, Clostridium chauvoei, Clostridium citroniae, Clostridium clariflavum, Clostridium clostridiiformes, Clostridium clostridioforme, Clostridium coccoides, Clostridium cochlearium, Clostridium cocleatum, Clostridium colicanis, Clostridium colinum, Clostridium difficile, Clostridium disporicum, Clostridium estertheticum, Clostridium fallax, Clostridium favososporum, Clostridium felsineum, Clostridium frigidicarnis, Clostridium gasigenes, Clostridium ghonii, Clostridium glycolicum, Clostridium glycyrrhizinilyticum, Clostridium haemolyticum, Clostridium hathewayi, Clostridium hiranonis, Clostridium histolyticum, Clostridium hylemonae, Clostridium indolis, Clostridium innocuum, Clostridium irregulare, Clostridium isatidis, Clostridium kluyveri, Clostridium lactatifermentans, Clostridium lavalense, Clostridium leptum, Clostridium limosum, Clostridium magnum, Clostridium malenominatum, Clostridium mayombei, Clostridium methylpentosum, Clostridium nexile, Clostridium novyi, Clostridium orbiscindens, Clostridium oroticum, Clostridium paraputrificum, Clostridium perfringens, Clostridium phytofermentans, Clostridium piliforme, Clostridium putrefaciens, Clostridium quinii, Clostridium ramosum, Clostridium rectum, Clostridium saccharogumia, Clostridium saccharolyticum, Clostridium sardiniense, Clostridium sartagoforme, Clostridium scindens, Clostridium septicum, Clostridium sordellii, Clostridium sp.7_2_43FAA, Clostridium sp. D5, Clostridium sp. HGF2, Clostridium sp. HPB_46, Clostridium sp. JC122, Clostridium sp. L2_50, Clostridium sp. LMG 16094, Clostridium sp. M62_1, Clostridium sp. MLG055, Clostridium sp. MT4 E, Clostridium sp. NMBHI_1, Clostridium sp. NML 04A032, Clostridium sp. SS2_1, Clostridium sp. SY8519, Clostridium sp. TM_40, Clostridium sp. YIT 12069, Clostridium sp. YIT 12070, Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium sporosphaeroides, Clostridium stercorarium, Clostridium sticklandii, Clostridium straminisolvens, Clostridium subterminale, Clostridium sulfidigenes, Clostridium symbiosum, Clostridium tertium, Clostridium tetani, Clostridium thermocellum, Clostridium tyrobutyricum, Clostridium viride, Clostridium xylanolyticum, Collinsella aerofaciens, Collinsella intestinalis, Collinsella stercoris, Collinsella tanakaei, Comamonadaceae bacterium NML000135, Comamonadaceae bacterium NML790751, Comamonadaceae bacterium NML910035, Comamonadaceae bacterium NML910036, Comamonadaceae bacterium oral taxon F47, Comamonas sp. NSP5, Conchiformibius kuhniae, Coprobacillus cateniformis, Coprobacillus sp.29_1, Coprobacillus sp. D7, Coprococcus catus, Coprococcus comes, Coprococcus eutactus, Coprococcus sp. ART55_1, Coriobacteriaceae bacterium BV3Ac1, 79 FH12512877.6 Attorney Docket No.: NEX-16225 Coriobacteriaceae bacterium JC110, Coriobacteriaceae bacterium phI, Corynebacterium accolens, Corynebacterium ammoniagenes, Corynebacterium amycolatum, Corynebacterium appendicis, Corynebacterium argentoratense, Corynebacterium atypicum, Corynebacterium aurimucosum, Corynebacterium bovis, Corynebacterium canis, Corynebacterium casei, Corynebacterium confusum, Corynebacterium coyleae, Corynebacterium diphtheriae, Corynebacterium durum, Corynebacterium efficiens, Corynebacterium falsenii, Corynebacterium flavescens, Corynebacterium genitalium, Corynebacterium glaucum, Corynebacterium glucuronolyticum, Corynebacterium glutamicum, Corynebacterium hansenii, Corynebacterium imitans, Corynebacterium jeikeium, Corynebacterium kroppenstedtii, Corynebacterium lipophiloflavum, Corynebacterium macginleyi, Corynebacterium mastitidis, Corynebacterium matruchotii, Corynebacterium minutissimum, Corynebacterium mucifaciens, Corynebacterium propinquum, Corynebacterium pseudodiphtheriticum, Corynebacterium pseudogenitalium, Corynebacterium pseudotuberculosis, Corynebacterium pyruviciproducens, Corynebacterium renale, Corynebacterium resistens, Corynebacterium riegelii, Corynebacterium simulans, Corynebacterium singulare, Corynebacterium sp.1 ex sheep, Corynebacterium sp. L_2012475, Corynebacterium sp. NML 93_0481, Corynebacterium sp. NML 97_0186, Corynebacterium sp. NML 99_0018, Corynebacterium striatum, Corynebacterium sundsvallense, Corynebacterium tuberculostearicum, Corynebacterium tuscaniae, Corynebacterium ulcerans, Corynebacterium urealyticum, Corynebacterium ureicelerivorans, Corynebacterium variabile, Corynebacterium xerosis, Coxiella burnetii, Cronobacter malonaticus, Cronobacter sakazakii, Cronobacter turicensis, Cryptobacterium curtum, Cupriavidus metallidurans, Cytophaga xylanolytica, Deferribacteres sp. oral clone JV001, Deferribacteres sp. oral clone JV006, Deferribacteres sp. oral clone JV023, Deinococcus radiodurans, Deinococcus sp. R_43890, Delftia acidovorans, Dermabacter hominis, Dermacoccus sp. Ellin185, Desmospora activa, Desmospora sp.8437, Desulfitobacterium frappieri, Desulfitobacterium hafniense, Desulfobulbus sp. oral clone CH031, Desulfotomaculum nigrificans, Desulfovibrio desulfuricans, Desulfovibrio fairfieldensis, Desulfovibrio piger, Desulfovibrio sp.3_1_syn3, Desulfovibrio vulgaris, Dialister invisus, Dialister micraerophilus, Dialister microaerophilus, Dialister pneumosintes, Dialister propionicifaciens, Dialister sp. oral taxon 502, Dialister succinatiphilus, Dietzia natronolimnaea, Dietzia sp. BBDP51, Dietzia sp. CA149, Dietzia timorensis, Dorea formicigenerans, Dorea longicatena, Dysgonomonas gadei, Dysgonomonas mossii, Edwardsiella tarda, Eggerthella lenta, Eggerthella sinensis, 80 FH12512877.6 Attorney Docket No.: NEX-16225 Eggerthella sp.1_3_56FAA, Eggerthella sp. HGA1, Eggerthella sp. YY7918, Ehrlichia chaffeensis, Eikenella corrodens, Enhydrobacter aerosaccus, Enterobacter aerogenes, Enterobacter asburiae, Enterobacter cancerogenus, Enterobacter cloacae, Enterobacter cowanii, Enterobacter hormaechei, Enterobacter sp.247BMC, Enterobacter sp.638, Enterobacter sp. JC163, Enterobacter sp. SCSS, Enterobacter sp. TSE38, Enterobacteriaceae bacterium 9_2_54FAA, Enterobacteriaceae bacterium CF01Ent_1, Enterobacteriaceae bacterium Smarlab 3302238, Enterococcus avium, Enterococcus caccae, Enterococcus casseliflavus, Enterococcus durans, Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, Enterococcus gilvus, Enterococcus hawaiiensis, Enterococcus hirae, Enterococcus italicus, Enterococcus mundtii, Enterococcus raffinosus, Enterococcus sp. BV2CASA2, Enterococcus sp. CCRI_16620, Enterococcus sp. F95, Enterococcus sp. RfL6, Enterococcus thailandicus, Eremococcus coleocola, Erysipelothrix inopinata, Erysipelothrix rhusiopathiae, Erysipelothrix tonsillarum, Erysipelotrichaceae bacterium 3_1_53, Erysipelotrichaceae bacterium 5_2_54FAA, Escherichia albertii, Escherichia coli, Escherichia fergusonii, Escherichia hermannii, Escherichia sp.1_1_43, Escherichia sp. 4_1_40B, Escherichia sp. B4, Escherichia vulneris, Ethanoligenens harbinense, Eubacteriaceae bacterium P4P_50 P4, Eubacterium barkeri, Eubacterium biforme, Eubacterium brachy, Eubacterium budayi, Eubacterium callanderi, Eubacterium cellulosolvens, Eubacterium contortum, Eubacterium coprostanoligenes, Eubacterium cylindroides, Eubacterium desmolans, Eubacterium dolichum, Eubacterium eligens, Eubacterium fissicatena, Eubacterium hadrum, Eubacterium hallii, Eubacterium infirmum, Eubacterium limosum, Eubacterium moniliforme, Eubacterium multiforme, Eubacterium nitritogenes, Eubacterium nodatum, Eubacterium ramulus, Eubacterium rectale, Eubacterium ruminantium, Eubacterium saburreum, Eubacterium saphenum, Eubacterium siraeum, Eubacterium sp.3_1_31, Eubacterium sp. AS15b, Eubacterium sp. OBRC9, Eubacterium sp. oral clone GI038, Eubacterium sp. oral clone IR009, Eubacterium sp. oral clone JH012, Eubacterium sp. oral clone JI012, Eubacterium sp. oral clone JN088, Eubacterium sp. oral clone JS001, Eubacterium sp. oral clone OH3A, Eubacterium sp. WAL 14571, Eubacterium tenue, Eubacterium tortuosum, Eubacterium ventriosum, Eubacterium xylanophilum, Eubacterium yurii, Ewingella americana, Exiguobacterium acetylicum, Facklamia hominis, Faecalibacterium prausnitzii, Filifactor alocis, Filifactor villosus, Finegoldia magna, Flavobacteriaceae genomosp. C1, Flavobacterium sp. NF2_1, Flavonifractor plautii, Flexispira rappini, Flexistipes sinusarabici, Francisella novicida, Francisella philomiragia, Francisella tularensis, Fulvimonas sp. NML 060897, 81 FH12512877.6 Attorney Docket No.: NEX-16225 Fusobacterium canifelinum, Fusobacterium genomosp. C1, Fusobacterium genomosp. C2, Fusobacterium gonidiaformans, Fusobacterium mortiferum, Fusobacterium naviforme, Fusobacterium necrogenes, Fusobacterium necrophorum, Fusobacterium nucleatum, Fusobacterium periodonticum, Fusobacterium russii, Fusobacterium sp.1_1_41FAA, Fusobacterium sp.11_3_2, Fusobacterium sp.12_1B, Fusobacterium sp.2_1_31, Fusobacterium sp.3_1_27, Fusobacterium sp.3_1_33, Fusobacterium sp.3_1_36A2, Fusobacterium sp.3_1_5R, Fusobacterium sp. AC18, Fusobacterium sp. ACB2, Fusobacterium sp. AS2, Fusobacterium sp. CM1, Fusobacterium sp. CM21, Fusobacterium sp. CM22, Fusobacterium sp. D12, Fusobacterium sp. oral clone ASCF06, Fusobacterium sp. oral clone ASCF11, Fusobacterium ulcerans, Fusobacterium varium, Gardnerella vaginalis, Gemella haemolysans, Gemella morbillorum, Gemella morbillorum, Gemella sanguinis, Gemella sp. oral clone ASCE02, Gemella sp. oral clone ASCF04, Gemella sp. oral clone ASCF12, Gemella sp. WAL 1945J, Gemmiger formicilis, Geobacillus kaustophilus, Geobacillus sp. E263, Geobacillus sp. WCH70, Geobacillus stearothermophilus, Geobacillus thermocatenulatus, Geobacillus thermodenitrificans, Geobacillus thermoglucosidasius, Geobacillus thermoleovorans, Geobacter bemidjiensis, Gloeobacter violaceus, Gluconacetobacter azotocaptans, Gluconacetobacter diazotrophicus, Gluconacetobacter entanii, Gluconacetobacter europaeus, Gluconacetobacter hansenii, Gluconacetobacter johannae, Gluconacetobacter oboediens, Gluconacetobacter xylinus, Gordonia bronchialis, Gordonia polyisoprenivorans, Gordonia sp. KTR9, Gordonia sputi, Gordonia terrae, Gordonibacter pamelaeae, Gordonibacter pamelaeae, Gracilibacter thermotolerans, Gramella forsetii, Granulicatella adiacens, Granulicatella elegans, Granulicatella paradiacens, Granulicatella sp. M658_99_3, Granulicatella sp. oral clone ASC02, Granulicatella sp. oral clone ASCA05, Granulicatella sp. oral clone ASCB09, Granulicatella sp. oral clone ASCG05, Grimontia hollisae, Haematobacter sp. BC14248, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus genomosp. P2 oral clone MB3_C24, Haemophilus genomosp. P3 oral clone MB3_C38, Haemophilus haemolyticus, Haemophilus influenzae, Haemophilus parahaemolyticus, Haemophilus parainfluenzae, Haemophilus paraphrophaemolyticus, Haemophilus parasuis, Haemophilus somnus, Haemophilus sp. 70334, Haemophilus sp. HK445, Haemophilus sp. oral clone ASCA07, Haemophilus sp. oral clone ASCG06, Haemophilus sp. oral clone BJ021, Haemophilus sp. oral clone BJ095, Haemophilus sp. oral clone JM053, Haemophilus sp. oral taxon 851, Haemophilus sputorum, Hafnia alvei, Halomonas elongata, Halomonas johnsoniae, Halorubrum lipolyticum, Helicobacter bilis, Helicobacter canadensis, Helicobacter cinaedi, Helicobacter pullorum, 82 FH12512877.6 Attorney Docket No.: NEX-16225 Helicobacter pylori, Helicobacter sp. None, Helicobacter winghamensis, Heliobacterium modesticaldum, Herbaspirillum seropedicae, Herbaspirillum sp. JC206, Histophilus somni, Holdemania filiformis, Hydrogenoanaerobacterium saccharovorans, Hyperthermus butylicus, Hyphomicrobium sulfonivorans, Hyphomonas neptunium, Ignatzschineria indica, Ignatzschineria sp. NML 95_0260, Ignicoccus islandicus, Inquilinus limosus, Janibacter limosus, Janibacter melonis, Janthinobacterium sp. SY12, Johnsonella ignava, Jonquetella anthropi, Kerstersia gyiorum, Kingella denitrificans, Kingella genomosp. P1 oral cone MB2_C20, Kingella kingae, Kingella oralis, Kingella sp. oral clone ID059, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella sp. AS10, Klebsiella sp. Co9935, Klebsiella sp. enrichment culture clone SRC_DSD25, Klebsiella sp. OBRC7, Klebsiella sp. SP_BA, Klebsiella sp. SRC_DSD1, Klebsiella sp. SRC_DSD11, Klebsiella sp. SRC_DSD12, Klebsiella sp. SRC_DSD15, Klebsiella sp. SRC_DSD2, Klebsiella sp. SRC_DSD6, Klebsiella variicola, Kluyvera ascorbata, Kluyvera cryocrescens, Kocuria marina, Kocuria palustris, Kocuria rhizophila, Kocuria rosea, Kocuria varians, Lachnobacterium bovis, Lachnospira multipara, Lachnospira pectinoschiza, Lachnospiraceae bacterium 1_1_57FAA, Lachnospiraceae bacterium 1_4_56FAA, Lachnospiraceae bacterium 2_1_46FAA, Lachnospiraceae bacterium 2_1_58FAA, Lachnospiraceae bacterium 3_1_57FAA_CT1, Lachnospiraceae bacterium 4_1_37FAA, Lachnospiraceae bacterium 5_1_57FAA, Lachnospiraceae bacterium 5_1_63FAA, Lachnospiraceae bacterium 6_1_63FAA, Lachnospiraceae bacterium 8_1_57FAA, Lachnospiraceae bacterium 9_1_43BFAA, Lachnospiraceae bacterium A4, Lachnospiraceae bacterium DJF VP30, Lachnospiraceae bacterium ICM62, Lachnospiraceae bacterium MSX33, Lachnospiraceae bacterium oral taxon 107, Lachnospiraceae bacterium oral taxon F15, Lachnospiraceae genomosp. C1, Lactobacillus acidipiscis, Lactobacillus acidophilus, Lactobacillus alimentarius, Lactobacillus amylolyticus, Lactobacillus amylovorus, Lactobacillus antri, Lactobacillus brevis, Lactobacillus buchneri, Lactobacillus casei, Lactobacillus catenaformis, Lactobacillus coleohominis, Lactobacillus coryniformis, Lactobacillus crispatus, Lactobacillus curvatus, Lactobacillus delbrueckii, Lactobacillus dextrinicus, Lactobacillus farciminis, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus gastricus, Lactobacillus genomosp. C1, Lactobacillus genomosp. C2, Lactobacillus helveticus, Lactobacillus hilgardii, Lactobacillus hominis, Lactobacillus iners, Lactobacillus jensenii, Lactobacillus johnsonii, Lactobacillus kalixensis, Lactobacillus kefiranofaciens, Lactobacillus kefiri, Lactobacillus kimchii, Lactobacillus leichmannii, Lactobacillus mucosae, Lactobacillus murinus, Lactobacillus nodensis, Lactobacillus oeni, Lactobacillus 83 FH12512877.6 Attorney Docket No.: NEX-16225 oris, Lactobacillus parabrevis, Lactobacillus parabuchneri, Lactobacillus paracasei, Lactobacillus parakefiri, Lactobacillus pentosus, Lactobacillus perolens, Lactobacillus plantarum, Lactobacillus pontis, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus rogosae, Lactobacillus ruminis, Lactobacillus sakei, Lactobacillus salivarius, Lactobacillus saniviri, Lactobacillus senioris, Lactobacillus sp.66c, Lactobacillus sp. BT6, Lactobacillus sp. KLDS 1.0701, Lactobacillus sp. KLDS 1.0702, Lactobacillus sp. KLDS 1.0703, Lactobacillus sp. KLDS 1.0704, Lactobacillus sp. KLDS 1.0705, Lactobacillus sp. KLDS 1.0707, Lactobacillus sp. KLDS 1.0709, Lactobacillus sp. KLDS 1.0711, Lactobacillus sp. KLDS 1.0712, Lactobacillus sp. KLDS 1.0713, Lactobacillus sp. KLDS 1.0716, Lactobacillus sp. KLDS 1.0718, Lactobacillus sp. KLDS 1.0719, Lactobacillus sp. oral clone HT002, Lactobacillus sp. oral clone HT070, Lactobacillus sp. oral taxon 052, Lactobacillus tucceti, Lactobacillus ultunensis, Lactobacillus vaginalis, Lactobacillus vini, Lactobacillus vitulinus, Lactobacillus zeae, Lactococcus garvieae, Lactococcus lactis, Lactococcus raffinolactis, Lactonifactor longoviformis, Laribacter hongkongensis, Lautropia mirabilis, Lautropia sp. oral clone AP009, Legionella hackeliae, Legionella longbeachae, Legionella pneumophila, Legionella sp. D3923, Legionella sp. D4088, Legionella sp. H63, Legionella sp. NML 93L054, Legionella steelei, Leminorella grimontii, Leminorella richardii, Leptospira borgpetersenii, Leptospira broomii, Leptospira interrogans, Leptospira licerasiae, Leptotrichia buccalis, Leptotrichia genomosp. C1, Leptotrichia goodfellowii, Leptotrichia hofstadii, Leptotrichia shahii, Leptotrichia sp. neutropenicPatient, Leptotrichia sp. oral clone GT018, Leptotrichia sp. oral clone GT020, Leptotrichia sp. oral clone HE012, Leptotrichia sp. oral clone IK040, Leptotrichia sp. oral clone P2PB_51 P1, Leptotrichia sp. oral taxon 223, Leuconostoc carnosum, Leuconostoc citreum, Leuconostoc gasicomitatum, Leuconostoc inhae, Leuconostoc kimchii, Leuconostoc lactis, Leuconostoc mesenteroides, Leuconostoc pseudomesenteroides, Listeria grayi, Listeria innocua, Listeria ivanovii, Listeria monocytogenes, Listeria welshimeri, Luteococcus sanguinis, Lutispora thermophila, Lysinibacillus fusiformis, Lysinibacillus sphaericus, Macrococcus caseolyticus, Mannheimia haemolytica, Marvinbryantia formatexigens, Massilia sp. CCUG 43427A, Megamonas funiformis, Megamonas hypermegale, Megasphaera elsdenii, Megasphaera genomosp. C1, Megasphaera genomosp. type_1, Megasphaera micronuciformis, Megasphaera sp. BLPYG_07, Megasphaera sp. UPII 199_6, Metallosphaera sedula, Methanobacterium formicicum, Methanobrevibacter acididurans, Methanobrevibacter arboriphilus, Methanobrevibacter curvatus, Methanobrevibacter cuticularis, Methanobrevibacter filiformis, Methanobrevibacter gottschalkii, Methanobrevibacter millerae, 84 FH12512877.6 Attorney Docket No.: NEX-16225 Methanobrevibacter olleyae, Methanobrevibacter oralis, Methanobrevibacter ruminantium, Methanobrevibacter smithii, Methanobrevibacter thaueri, Methanobrevibacter woesei, Methanobrevibacter wolinii, Methanosphaera stadtmanae, Methylobacterium extorquens, Methylobacterium podarium, Methylobacterium radiotolerans, Methylobacterium sp.1sub, Methylobacterium sp. MM4, Methylocella silvestris, Methylophilus sp. ECd5, Microbacterium chocolatum, Microbacterium flavescens, Microbacterium gubbeenense, Microbacterium lacticum, Microbacterium oleivorans, Microbacterium oxydans, Microbacterium paraoxydans, Microbacterium phyllosphaerae, Microbacterium schleiferi, Microbacterium sp.768, Microbacterium sp. oral strain C24KA, Microbacterium testaceum, Micrococcus antarcticus, Micrococcus luteus, Micrococcus lylae, Micrococcus sp.185, Microcystis aeruginosa, Mitsuokella jalaludinii, Mitsuokella multacida, Mitsuokella sp. oral taxon 521, Mitsuokella sp. oral taxon G68, Mobiluncus curtisii, Mobiluncus mulieris, Moellerella wisconsensis, Mogibacterium diversum, Mogibacterium neglectum, Mogibacterium pumilum, Mogibacterium timidum, Mollicutes bacterium pACH93, Moorella thermoacetica, Moraxella catarrhalis, Moraxella lincolnii, Moraxella osloensis, Moraxella sp.16285, Moraxella sp. GM2, Morganella morganii, Morganella sp. JB_T16, Morococcus cerebrosus, Moryella indoligenes, Mycobacterium abscessus, Mycobacterium africanum, Mycobacterium alsiensis, Mycobacterium avium, Mycobacterium chelonae, Mycobacterium colombiense, Mycobacterium elephantis, Mycobacterium gordonae, Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium lacus, Mycobacterium leprae, Mycobacterium lepromatosis, Mycobacterium mageritense, Mycobacterium mantenii, Mycobacterium marinum, Mycobacterium microti, Mycobacterium neoaurum, Mycobacterium parascrofulaceum, Mycobacterium paraterrae, Mycobacterium phlei, Mycobacterium seoulense, Mycobacterium smegmatis, Mycobacterium sp.1761, Mycobacterium sp.1776, Mycobacterium sp.1781, Mycobacterium sp.1791, Mycobacterium sp.1797, Mycobacterium sp. AQ1GA4, Mycobacterium sp. B10_07.09.0206, Mycobacterium sp. GN_10546, Mycobacterium sp. GN_10827, Mycobacterium sp. GN_11124, Mycobacterium sp. GN_9188, Mycobacterium sp. GR_2007_210, Mycobacterium sp. HE5, Mycobacterium sp. NLA001000736, Mycobacterium sp. W, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycobacterium vulneris, Mycoplasma agalactiae, Mycoplasma amphoriforme, Mycoplasma arthritidis, Mycoplasma bovoculi, Mycoplasma faucium, Mycoplasma fermentans, Mycoplasma flocculare, Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma orale, Mycoplasma ovipneumoniae, Mycoplasma penetrans, Mycoplasma pneumoniae, Mycoplasma putrefaciens, Mycoplasma salivarium, 85 FH12512877.6 Attorney Docket No.: NEX-16225 Mycoplasmataceae genomosp. P1 oral clone MB1_G23, Myroides odoratimimus, Myroides sp. MY15, Neisseria bacilliformis, Neisseria cinerea, Neisseria elongata, Neisseria flavescens, Neisseria genomosp. P2 oral clone MB5_P15, Neisseria gonorrhoeae, Neisseria lactamica, Neisseria macacae, Neisseria meningitidis, Neisseria mucosa, Neisseria pharyngis, Neisseria polysaccharea, Neisseria sicca, Neisseria sp. KEM232, Neisseria sp. oral clone AP132, Neisseria sp. oral clone JC012, Neisseria sp. oral strain B33KA, Neisseria sp. oral taxon 014, Neisseria sp. SMC_A9199, Neisseria sp. TM10_1, Neisseria subflava, Neorickettsia risticii, Neorickettsia sennetsu, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica, Nocardia puris, Nocardia sp.01_Je_025, Nocardiopsis dassonvillei, Novosphingobium aromaticivorans, Oceanobacillus caeni, Oceanobacillus sp. Ndiop, Ochrobactrum anthropi, Ochrobactrum intermedium, Ochrobactrum pseudintermedium, Odoribacter laneus, Odoribacter splanchnicus, Okadaella gastrococcus, Oligella ureolytica, Oligella urethralis, Olsenella genomosp. C1, Olsenella profusa, Olsenella sp. F0004, Olsenella sp. oral taxon 809, Olsenella uli, Opitutus terrae, Oribacterium sinus, Oribacterium sp. ACB1, Oribacterium sp. ACB7, Oribacterium sp. CM12, Oribacterium sp. ICM51, Oribacterium sp. OBRC12, Oribacterium sp. oral taxon 078, Oribacterium sp. oral taxon 102, Oribacterium sp. oral taxon 108, Orientia tsutsugamushi, Ornithinibacillus bavariensis, Ornithinibacillus sp.7_10AIA, Oscillibacter sp. G2, Oscillibacter valericigenes, Oscillospira guilliermondii, Oxalobacter formigenes, Paenibacillus barcinonensis, Paenibacillus barengoltzii, Paenibacillus chibensis, Paenibacillus cookii, Paenibacillus durus, Paenibacillus glucanolyticus, Paenibacillus lactis, Paenibacillus lautus, Paenibacillus pabuli, Paenibacillus polymyxa, Paenibacillus popilliae, Paenibacillus sp. CIP 101062, Paenibacillus sp. HGF5, Paenibacillus sp. HGF7, Paenibacillus sp. JC66, Paenibacillus sp. oral taxon F45, Paenibacillus sp. R_27413, Paenibacillus sp. R_27422, Paenibacillus timonensis, Pantoea agglomerans, Pantoea ananatis, Pantoea brenneri, Pantoea citrea, Pantoea conspicua, Pantoea septica, Papillibacter cinnamivorans, Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides gordonii, Parabacteroides johnsonii, Parabacteroides merdae, Parabacteroides sp. D13, Parabacteroides sp. NS31_3, Parachlamydia sp. UWE25, Paracoccus denitrificans, Paracoccus marcusii, Paraprevotella clara, Paraprevotella xylaniphila, Parascardovia denticolens, Parasutterella excrementihominis, Parasutterella secunda, Parvimonas micra, Parvimonas sp. oral taxon 110, Pasteurella bettyae, Pasteurella dagmatis, Pasteurella multocida, Pediococcus acidilactici, Pediococcus pentosaceus, Peptococcus niger, Peptococcus sp. oral clone JM048, Peptococcus sp. oral taxon 167, 86 FH12512877.6 Attorney Docket No.: NEX-16225 Peptoniphilus asaccharolyticus, Peptoniphilus duerdenii, Peptoniphilus harei, Peptoniphilus indolicus, Peptoniphilus ivorii, Peptoniphilus lacrimalis, Peptoniphilus sp. gpac007, Peptoniphilus sp. gpac018A, Peptoniphilus sp. gpac077, Peptoniphilus sp. gpac148, Peptoniphilus sp. JC140, Peptoniphilus sp. oral taxon 386, Peptoniphilus sp. oral taxon 836, Peptostreptococcaceae bacterium ph1, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus sp.9succ1, Peptostreptococcus sp. oral clone AP24, Peptostreptococcus sp. oral clone FJ023, Peptostreptococcus sp. P4P_31 P3, Peptostreptococcus stomatis, Phascolarctobacterium faecium, Phascolarctobacterium sp. YIT 12068, Phascolarctobacterium succinatutens, Phenylobacterium zucineum, Photorhabdus asymbiotica, Pigmentiphaga daeguensis, Planomicrobium koreense, Plesiomonas shigelloides, Porphyromonadaceae bacterium NML 060648, Porphyromonas asaccharolytica, Porphyromonas endodontalis, Porphyromonas gingivalis, Porphyromonas levii, Porphyromonas macacae, Porphyromonas somerae, Porphyromonas sp. oral clone BB134, Porphyromonas sp. oral clone F016, Porphyromonas sp. oral clone P2PB_52 P1, Porphyromonas sp. oral clone P4GB_100 P2, Porphyromonas sp. UQD 301, Porphyromonas uenonis, Prevotella albensis, Prevotella amnii, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella buccae, Prevotella buccalis, Prevotella copri, Prevotella corporis, Prevotella dentalis, Prevotella denticola, Prevotella disiens, Prevotella genomosp. C1, Prevotella genomosp. C2, Prevotella genomosp. P7 oral clone MB2_P31, Prevotella genomosp. P8 oral clone MB3_P13, Prevotella genomosp. P9 oral clone MB7_G16, Prevotella heparinolytica, Prevotella histicola, Prevotella intermedia, Prevotella loescheii, Prevotella maculosa, Prevotella marshii, Prevotella melaninogenica, Prevotella micans, Prevotella multiformis, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oulorum, Prevotella pallens, Prevotella ruminicola, Prevotella salivae, Prevotella sp. BI_42, Prevotella sp. CM38, Prevotella sp. ICM1, Prevotella sp. ICM55, Prevotella sp. JCM 6330, Prevotella sp. oral clone AA020, Prevotella sp. oral clone ASCG10, Prevotella sp. oral clone ASCG12, Prevotella sp. oral clone AU069, Prevotella sp. oral clone CY006, Prevotella sp. oral clone DA058, Prevotella sp. oral clone FL019, Prevotella sp. oral clone FU048, Prevotella sp. oral clone FW035, Prevotella sp. oral clone GI030, Prevotella sp. oral clone GI032, Prevotella sp. oral clone GI059, Prevotella sp. oral clone GU027, Prevotella sp. oral clone HF050, Prevotella sp. oral clone ID019, Prevotella sp. oral clone IDR_CEC_0055, Prevotella sp. oral clone IK053, Prevotella sp. oral clone IK062, Prevotella sp. oral clone P4PB_83 P2, Prevotella sp. oral taxon 292, Prevotella sp. oral taxon 299, Prevotella sp. oral taxon 300, 87 FH12512877.6 Attorney Docket No.: NEX-16225 Prevotella sp. oral taxon 302, Prevotella sp. oral taxon 310, Prevotella sp. oral taxon 317, Prevotella sp. oral taxon 472, Prevotella sp. oral taxon 781, Prevotella sp. oral taxon 782, Prevotella sp. oral taxon F68, Prevotella sp. oral taxon G60, Prevotella sp. oral taxon G70, Prevotella sp. oral taxon G71, Prevotella sp. SEQ053, Prevotella sp. SEQ065, Prevotella sp. SEQ072, Prevotella sp. SEQ116, Prevotella sp. SG12, Prevotella sp. sp24, Prevotella sp. sp34, Prevotella stercorea, Prevotella tannerae, Prevotella timonensis, Prevotella veroralis, Prevotella jejuni, Prevotella aurantiaca, Prevotella baroniae, Prevotella colorans, Prevotella corporis, Prevotella dentasini, Prevotella enoeca, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella loescheii, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella oryzae, Prevotella paludivivens, Prevotella pleuritidis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella scopos, Prevotella shahii, Prevotella zoogleoformans, Prevotellaceae bacterium P4P_62 P1, Prochlorococcus marinus, Propionibacteriaceae bacterium NML 02_0265, Propionibacterium acidipropionici, Propionibacterium acnes, Propionibacterium avidum, Propionibacterium freudenreichii, Propionibacterium granulosum, Propionibacterium jensenii, Propionibacterium propionicum, Propionibacterium sp.434_HC2, Propionibacterium sp. H456, Propionibacterium sp. LG, Propionibacterium sp. oral taxon 192, Propionibacterium sp. S555a, Propionibacterium thoenii, Proteus mirabilis, Proteus penneri, Proteus sp. HS7514, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia rustigianii, Providencia stuartii, Pseudoclavibacter sp. Timone, Pseudoflavonifractor capillosus, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas gessardii, Pseudomonas mendocina, Pseudomonas monteilii, Pseudomonas poae, Pseudomonas pseudoalcaligenes, Pseudomonas putida, Pseudomonas sp.2_1_26, Pseudomonas sp. G1229, Pseudomonas sp. NP522b, Pseudomonas stutzeri, Pseudomonas tolaasii, Pseudomonas viridiflava, Pseudoramibacter alactolyticus, Psychrobacter arcticus, Psychrobacter cibarius, Psychrobacter cryohalolentis, Psychrobacter faecalis, Psychrobacter nivimaris, Psychrobacter pulmonis, Psychrobacter sp.13983, Pyramidobacter piscolens, Ralstonia pickettii, Ralstonia sp.5_7_47FAA, Raoultella ornithinolytica, Raoultella planticola, Raoultella terrigena, Rhodobacter sp. oral taxon C30, Rhodobacter sphaeroides, Rhodococcus corynebacterioides, Rhodococcus equi, Rhodococcus erythropolis, Rhodococcus fascians, Rhodopseudomonas palustris, Rickettsia akari, Rickettsia conorii, Rickettsia prowazekii, Rickettsia rickettsii, Rickettsia slovaca, Rickettsia typhi, Robinsoniella peoriensis, Roseburia cecicola, Roseburia faecalis, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Roseburia inulinivorans, Roseburia sp.11SE37, Roseburia sp. 88 FH12512877.6 Attorney Docket No.: NEX-16225 11SE38, Roseiflexus castenholzii, Roseomonas cervicalis, Roseomonas mucosa, Roseomonas sp. NML94_0193, Roseomonas sp. NML97_0121, Roseomonas sp. NML98_0009, Roseomonas sp. NML98_0157, Rothia aeria, Rothia dentocariosa, Rothia mucilaginosa, Rothia nasimurium, Rothia sp. oral taxon 188, Ruminobacter amylophilus, Ruminococcaceae bacterium D16, Ruminococcus albus, Ruminococcus bromii, Ruminococcus callidus, Ruminococcus champanellensis, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus hansenii, Ruminococcus lactaris, Ruminococcus obeum, Ruminococcus sp. 18P13, Ruminococcus sp.5_1_39BFAA, Ruminococcus sp.9SE51, Ruminococcus sp. ID8, Ruminococcus sp. K_1, Ruminococcus torques, Saccharomonospora viridis, Salmonella bongori, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella enterica, Salmonella typhimurium, Salmonella typhimurium, Sarcina ventriculi, Scardovia inopinata, Scardovia wiggsiae, Segniliparus rotundus, Segniliparus rugosus, Selenomonas artemidis, Selenomonas dianae, Selenomonas flueggei, Selenomonas genomosp. C1, Selenomonas genomosp. C2, Selenomonas genomosp. P5, Selenomonas genomosp. P6 oral clone MB3_C41, Selenomonas genomosp. P7 oral clone MB5_C08, Selenomonas genomosp. P8 oral clone MB5_P06, Selenomonas infelix, Selenomonas noxia, Selenomonas ruminantium, Selenomonas sp. FOBRC9, Selenomonas sp. oral clone FT050, Selenomonas sp. oral clone GI064, Selenomonas sp. oral clone GT010, Selenomonas sp. oral clone HU051, Selenomonas sp. oral clone IK004, Selenomonas sp. oral clone IQ048, Selenomonas sp. oral clone JI021, Selenomonas sp. oral clone JS031, Selenomonas sp. oral clone OH4A, Selenomonas sp. oral clone P2PA_80 P4, Selenomonas sp. oral taxon 137, Selenomonas sp. oral taxon 149, Selenomonas sputigena, Serratia fonticola, Serratia liquefaciens, Serratia marcescens, Serratia odorifera, Serratia proteamaculans, Shewanella putrefaciens, Shigella boydii, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Shuttleworthia satelles, Shuttleworthia sp. MSX8B, Shuttleworthia sp. oral taxon G69, Simonsiella muelleri, Slackia equolifaciens, Slackia exigua, Slackia faecicanis, Slackia heliotrinireducens, Slackia isoflavoniconvertens, Slackia piriformis, Slackia sp. NATTS, Solobacterium moorei, Sphingobacterium faecium, Sphingobacterium mizutaii, Sphingobacterium multivorum, Sphingobacterium spiritivorum, Sphingomonas echinoides, Sphingomonas sp. oral clone FI012, Sphingomonas sp. oral clone FZ016, Sphingomonas sp. oral taxon A09, Sphingomonas sp. oral taxon F71, Sphingopyxis alaskensis, Spiroplasma insolitum, Sporobacter termitidis, Sporolactobacillus inulinus, Sporolactobacillus nakayamae, 89 FH12512877.6 Attorney Docket No.: NEX-16225 Sporosarcina newyorkensis, Sporosarcina sp.2681, Staphylococcaceae bacterium NML 92_0017, Staphylococcus aureus, Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus carnosus, Staphylococcus cohnii, Staphylococcus condimenti, Staphylococcus epidermidis, Staphylococcus equorum, Staphylococcus fleurettii, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pasteuri, Staphylococcus pseudintermedius, Staphylococcus saccharolyticus, Staphylococcus saprophyticus, Staphylococcus sciuri, Staphylococcus sp. clone bottae7, Staphylococcus sp. H292, Staphylococcus sp. H780, Staphylococcus succinus, Staphylococcus vitulinus, Staphylococcus warneri, Staphylococcus xylosus, Stenotrophomonas maltophilia, Stenotrophomonas sp. FG_6, Streptobacillus moniliformis, Streptococcus agalactiae, Streptococcus alactolyticus, Streptococcus anginosus, Streptococcus australis, Streptococcus bovis, Streptococcus canis, Streptococcus constellatus, Streptococcus cristatus, Streptococcus downei, Streptococcus dysgalactiae, Streptococcus equi, Streptococcus equinus, Streptococcus gallolyticus, Streptococcus genomosp. C1, Streptococcus genomosp. C2, Streptococcus genomosp. C3, Streptococcus genomosp. C4, Streptococcus genomosp. C5, Streptococcus genomosp. C6, Streptococcus genomosp. C7, Streptococcus genomosp. C8, Streptococcus gordonii, Streptococcus infantarius, Streptococcus infantis, Streptococcus intermedius, Streptococcus lutetiensis, Streptococcus massiliensis, Streptococcus milleri, Streptococcus mitis, Streptococcus mutans, Streptococcus oligofermentans, Streptococcus oralis, Streptococcus parasanguinis, Streptococcus pasteurianus, Streptococcus peroris, Streptococcus pneumoniae, Streptococcus porcinus, Streptococcus pseudopneumoniae, Streptococcus pseudoporcinus, Streptococcus pyogenes, Streptococcus ratti, Streptococcus salivarius, Streptococcus sanguinis, Streptococcus sinensis, Streptococcus sp.16362, Streptococcus sp.2_1_36FAA, Streptococcus sp.2285_97, Streptococcus sp.69130, Streptococcus sp. AC15, Streptococcus sp. ACS2, Streptococcus sp. AS20, Streptococcus sp. BS35a, Streptococcus sp. C150, Streptococcus sp. CM6, Streptococcus sp. CM7, Streptococcus sp. ICM10, Streptococcus sp. ICM12, Streptococcus sp. ICM2, Streptococcus sp. ICM4, Streptococcus sp. ICM45, Streptococcus sp. M143, Streptococcus sp. M334, Streptococcus sp. OBRC6, Streptococcus sp. oral clone ASB02, Streptococcus sp. oral clone ASCA03, Streptococcus sp. oral clone ASCA04, Streptococcus sp. oral clone ASCA09, Streptococcus sp. oral clone ASCB04, Streptococcus sp. oral clone ASCB06, Streptococcus sp. oral clone ASCC04, Streptococcus sp. oral clone ASCC05, Streptococcus sp. oral clone ASCC12, Streptococcus sp. oral clone ASCD01, Streptococcus sp. oral clone ASCD09, Streptococcus sp. oral clone ASCD10, 90 FH12512877.6 Attorney Docket No.: NEX-16225 Streptococcus sp. oral clone ASCE03, Streptococcus sp. oral clone ASCE04, Streptococcus sp. oral clone ASCE05, Streptococcus sp. oral clone ASCE06, Streptococcus sp. oral clone ASCE09, Streptococcus sp. oral clone ASCE10, Streptococcus sp. oral clone ASCE12, Streptococcus sp. oral clone ASCF05, Streptococcus sp. oral clone ASCF07, Streptococcus sp. oral clone ASCF09, Streptococcus sp. oral clone ASCG04, Streptococcus sp. oral clone BW009, Streptococcus sp. oral clone CH016, Streptococcus sp. oral clone GK051, Streptococcus sp. oral clone GM006, Streptococcus sp. oral clone P2PA_41 P2, Streptococcus sp. oral clone P4PA_30 P4, Streptococcus sp. oral taxon 071, Streptococcus sp. oral taxon G59, Streptococcus sp. oral taxon G62, Streptococcus sp. oral taxon G63, Streptococcus sp. SHV515, Streptococcus suis, Streptococcus thermophilus, Streptococcus uberis, Streptococcus urinalis, Streptococcus vestibularis, Streptococcus viridans, Streptomyces albus, Streptomyces griseus, Streptomyces sp.1 AIP_2009, Streptomyces sp. SD 511, Streptomyces sp. SD 524, Streptomyces sp. SD 528, Streptomyces sp. SD 534, Streptomyces thermoviolaceus, Subdoligranulum variabile, Succinatimonas hippei, Sutterella morbirenis, Sutterella parvirubra, Sutterella sanguinus, Sutterella sp. YIT 12072, Sutterella stercoricanis, Sutterella wadsworthensis, Synergistes genomosp. C1, Synergistes sp. RMA 14551, Synergistetes bacterium ADV897, Synergistetes bacterium LBVCM1157, Synergistetes bacterium oral taxon 362, Synergistetes bacterium oral taxon D48, Syntrophococcus sucromutans, Syntrophomonadaceae genomosp. P1, Tannerella forsythia, Tannerella sp.6_1_58FAA_CT1, Tatlockia micdadei, Tatumella ptyseos, Tessaracoccus sp. oral taxon F04, Tetragenococcus halophilus, Tetragenococcus koreensis, Thermoanaerobacter pseudethanolicus, Thermobifida fusca, Thermofilum pendens, Thermus aquaticus, Tissierella praeacuta, Trabulsiella guamensis, Treponema denticola, Treponema genomosp. P1, Treponema genomosp. P4 oral clone MB2_G19, Treponema genomosp. P5 oral clone MB3_P23, Treponema genomosp. P6 oral clone MB4_G11, Treponema lecithinolyticum, Treponema pallidum, Treponema parvum, Treponema phagedenis, Treponema putidum, Treponema refringens, Treponema socranskii, Treponema sp. 6:H:D15A_4, Treponema sp. clone DDKL_4, Treponema sp. oral clone JU025, Treponema sp. oral clone JU031, Treponema sp. oral clone P2PB_53 P3, Treponema sp. oral taxon 228, Treponema sp. oral taxon 230, Treponema sp. oral taxon 231, Treponema sp. oral taxon 232, Treponema sp. oral taxon 235, Treponema sp. oral taxon 239, Treponema sp. oral taxon 247, Treponema sp. oral taxon 250, Treponema sp. oral taxon 251, Treponema sp. oral taxon 254, Treponema sp. oral taxon 265, Treponema sp. oral taxon 270, Treponema sp. oral taxon 271, Treponema sp. oral taxon 508, Treponema sp. oral taxon 518, Treponema sp. oral taxon 91 FH12512877.6 Attorney Docket No.: NEX-16225 G85, Treponema sp. ovine footrot, Treponema vincentii, Tropheryma whipplei, Trueperella pyogenes, Tsukamurella paurometabola, Tsukamurella tyrosinosolvens, Turicibacter sanguinis, Ureaplasma parvum, Ureaplasma urealyticum, Ureibacillus composti, Ureibacillus suwonensis, Ureibacillus terrenus, Ureibacillus thermophilus, Ureibacillus thermosphaericus, Vagococcus fluvialis, Veillonella atypica, Veillonella dispar, Veillonella genomosp. P1 oral clone MB5_P17, Veillonella montpellierensis, Veillonella parvula, Veillonella sp.3_1_44, Veillonella sp.6_1_27, Veillonella sp. ACP1, Veillonella sp. AS16, Veillonella sp. BS32b, Veillonella sp. ICM51a, Veillonella sp. MSA12, Veillonella sp. NVG 100cf, Veillonella sp. OK11, Veillonella sp. oral clone ASCA08, Veillonella sp. oral clone ASCB03, Veillonella sp. oral clone ASCG01, Veillonella sp. oral clone ASCG02, Veillonella sp. oral clone OH1A, Veillonella sp. oral taxon 158, Veillonellaceae bacterium oral taxon 131, Veillonellaceae bacterium oral taxon 155, Vibrio cholerae, Vibrio fluvialis, Vibrio furnissii, Vibrio mimicus, Vibrio parahaemolyticus, Vibrio sp. RC341, Vibrio vulnificus, Victivallaceae bacterium NML 080035, Victivallis vadensis, Virgibacillus proomii, Weissella beninensis, Weissella cibaria, Weissella confusa, Weissella hellenica, Weissella kandleri, Weissella koreensis, Weissella paramesenteroides, Weissella sp. KLDS 7.0701, Wolinella succinogenes, Xanthomonadaceae bacterium NML 03_0222, Xanthomonas campestris, Xanthomonas sp. kmd_489, Xenophilus aerolatus, Yersinia aldovae, Yersinia aleksiciae, Yersinia bercovieri, Yersinia enterocolitica, Yersinia frederiksenii, Yersinia intermedia, Yersinia kristensenii, Yersinia mollaretii, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia rohdei, Yokenella regensburgei, Zimmermannella bifida, Zymomonas mobilis, Blautia massiliensis, Paraclostridium benzoelyticum, Dielma fastidiosa, Longicatena caecimuris , and Veillonella tobetsuensis. In some embodiments, the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium. In some embodiments, the bacterium is Escherichia coli strain Nissle, MG1655, or S1030. In some embodiments, the bacterium is an auxotroph in a gene that is important for cellular growth. Auxotrophy is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC) (Iwasaki T., et al. The Journal of Biochemistry, Volume 169, Issue 4, April 2021, Pages 387–394). An auxotroph is an organism that displays this characteristic. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth. 92 FH12512877.6 Attorney Docket No.: NEX-16225 As used herein, the term “essential gene” refers to a gene which is necessary to for cell growth and / or survival. Bacterial essential genes are well known to one of ordinary skill in the art, and can be identified by directed deletion of genes and / or random mutagenesis and screening (see, for example, Zhang and Lin, 2009, DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes, Nucl. Acids Res., 37:D455-D458 and Gerdes et al., Essential genes on metabolic maps, Curr. Opin. Biotechnol., 17(5):448-456, the entire contents of each of which are expressly incorporated herein by reference). An “essential gene” may be dependent on the circumstances and environment in which an organism lives. For example, a mutation of, modification of, or excision of an essential gene may result in the recombinant bacteria of the disclosure becoming an auxotroph. An auxotrophic modification is intended to cause bacteria to die in the absence of an exogenously added nutrient essential for survival or growth because they lack the gene(s) necessary to produce that essential nutrient. An auxotrophic modification is intended to cause bacteria to die in the absence of an exogenously added nutrient essential for survival or growth because they lack the gene(s) necessary to produce that essential nutrient. In some embodiments, any of the genetically engineered bacteria described herein also comprise a deletion or mutation in a gene required for cell survival and / or growth. In one embodiment, the essential gene is a DNA synthesis gene, for example, thyA. In another embodiment, the essential gene is a cell wall synthesis gene, for example, dapA. In yet another embodiment, the essential gene is an amino acid gene, for example, serA or MetA. Any gene required for cell survival and / or growth may be targeted, including but not limited to, cysE, glnA, ilvD, leuB, lysA, serA, metA, glyA, hisB, ilvA, pheA, proA, thrC, trpC, tyrA, thyA, uraA, dapA, dapB, dapD, dapE, dapF, flhD, metB, metC, proAB, and thi1, as long as the corresponding wild-type gene product is not produced in the bacteria. For example, thymine is a nucleic acid that is required for bacterial cell growth; in its absence, bacteria undergo cell death. The thyA gene encodes thimidylate synthetase, an enzyme that catalyzes the first step in thymine synthesis by converting dUMP to dTMP (Sat et al., 2003). In some embodiments, the bacterial cell of the disclosure is a thyA auxotroph in which the thyA gene is deleted and / or replaced with an unrelated gene. A thyA auxotroph can grow only when sufficient amounts of thymine are present, e.g., by adding thymine to growth media in vitro, or in the presence of high thymine levels found naturally in the human gut in vivo. In some embodiments, the bacterial cell of the disclosure is auxotrophic in a gene that is complemented when the bacterium is present in the mammalian gut. Without sufficient amounts of thymine, the thyA auxotroph dies. In some 93 FH12512877.6 Attorney Docket No.: NEX-16225 embodiments, the auxotrophic modification is used to ensure that the bacterial cell does not survive in the absence of the auxotrophic gene product (e.g., outside of the gut). In some embodiments, the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof. In some embodiments, wherein the bacterium comprises a kill switch. The kill switch is intended to actively kill engineered microbes in response to external stimuli. As opposed to an auxotrophic mutation where bacteria die because they lack an essential nutrient for survival, the kill switch is triggered by a particular factor in the environment that induces the production of toxic molecules within the microbe that cause cell death. Bacteria engineered with kill switches have been engineered for in vitro research purposes, e.g., to limit the spread of a biofuel-producing microorganism outside of a laboratory environment. Bacteria engineered for in vivo administration to treat a disease or disorder may also be programmed to die at a specific time after the expression and delivery of a heterologous gene or genes, for example, a therapeutic gene(s) or after the subject has experienced the therapeutic effect. For example, in some embodiments, the kill switch is activated to kill the bacteria after a period of time following oxygen level-dependent expression of argAfbr. In some embodiments, the kill switch is activated in a delayed fashion following oxygen level-dependent expression of argAfbr, for example, after the production of arginine or citrulline. Alternatively, the bacteria may be engineered to die after the bacteria has spread outside of a disease site. Specifically, it may be useful to prevent long-term colonization of subjects by the microorganism, spread of the microorganism outside the area of interest (for example, outside the gut) within the subject, or spread of the microorganism outside of the subject into the environment (for example, spread to the environment through the stool of the subject).Examples of such toxins that can be used in kill-switches include, but are not limited to, bacteriocins, lysins, and other molecules that cause cell death by lysing cell membranes, degrading cellular DNA, or other mechanisms. Such toxins can be used individually or in combination. The switches that control their production can be based on, for example, transcriptional activation (toggle switches; see, e.g., Gardner et al., 2000), translation (riboregulators), or DNA recombination (recombinase-based switches), and can sense environmental stimuli such as anaerobiosis or reactive oxygen species. These switches can be activated by a single environmental factor or may require several activators in AND, OR, NAND and NOR logic configurations to induce cell death. For example, an AND riboregulator switch is activated by tetracycline, isopropyl β-D-1-thiogalactopyranoside (IPTG), and arabinose to induce the expression of lysins, which permeabilize the cell 94 FH12512877.6 Attorney Docket No.: NEX-16225 membrane and kill the cell. IPTG induces the expression of the endolysin and holin mRNAs, which are then derepressed by the addition of arabinose and tetracycline. All three inducers must be present to cause cell death. Examples of kill switches are known in the art (Callura et al., 2010). In some embodiments, the kill switch is activated to kill the bacteria after a period of time following oxygen level-dependent expression of argAfbr. In some embodiments, the kill switch is activated in a delayed fashion following oxygen level-dependent expression of argAfbr. Kill-switches can be designed such that a toxin is produced in response to an environmental condition or external signal (e.g., the bacteria is killed in response to an external cue) or, alternatively designed such that a toxin is produced once an environmental condition no longer exists or an external signal is ceased. Pharmaceutical Compositions In certain aspects, provided herein are pharmaceutical compositions comprising the engineered microorganism described herein. In some embodiments, the bacterial formulation comprises a bacterium and / or a combination of bacteria described herein and a pharmaceutically acceptable carrier. In certain embodiments, at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the bacteria in the bacterial composition are the bacteria described herein. In certain embodiments, substantially all of the bacteria in the bacterial composition are the bacteria described herein. In certain embodiments, the bacterial composition comprises at least 1 x 103colony forming units (CFUs), 1 x 104colony forming units (CFUs), 1 x 105colony forming units (CFUs), 5 x 105colony forming units (CFUs), 1 x 106colony forming units (CFUs), 2 x 106colony forming units (CFUs), 3 x 106colony forming units (CFUs), 4 x 106colony forming units (CFUs), 5 x 106colony forming units (CFUs), 6 x 106colony forming units (CFUs), 7 x 106colony forming units (CFUs), 8 x 106colony forming units (CFUs), 9 x 106colony forming units (CFUs), 1 x 107colony forming units (CFUs), 2 x 107colony forming units (CFUs), 3 x 107colony forming units (CFUs), 4 x 107colony forming units (CFUs), 5 x 107colony forming units (CFUs), 6 x 107colony forming units (CFUs), 7 x 107colony forming units (CFUs), 8 x 107colony forming 95 FH12512877.6 Attorney Docket No.: NEX-16225 units (CFUs), 9 x 107colony forming units (CFUs), 1 x 108colony forming units (CFUs), 2 x 108colony forming units (CFUs), 3 x 108colony forming units (CFUs), 4 x 108colony forming units (CFUs), 5 x 108colony forming units (CFUs), 6 x 108colony forming units (CFUs), 7 x 108colony forming units (CFUs), 8 x 108colony forming units (CFUs), 9 x 108colony forming units (CFUs), 1 x 109colony forming units (CFUs), 5 x 109colony forming units (CFUs), 1 x 1010colony forming units (CFUs) 5 x 1010colony forming units (CFUs), 1 x 1011colony forming units (CFUs) 5 x 1011colony forming units (CFUs), 1 x 1012colony forming units (CFUs) 5 x 1012colony forming units (CFUs), 1 x 1013colony forming units (CFUs) of the bacteria described herein. The selected dosage level will depend upon a variety of factors including the subject’s diet, the route of administration, the time of administration, the residence time of the particular microorganism being employed, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular composition employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could prescribe and / or administer doses of the bacteria employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In some embodiments, probiotic formulations containing the bacteria described herein are provided as encapsulated, enteric coated, or powder forms, with doses ranging up to 1011cfu (e.g., up to 1010cfu). In some embodiments, the composition comprises 5 x 1011cfu of the bacteria described herein and 10% (w / w) corn starch in a capsule. In some embodiments, the capsule is enteric coated, e.g., for duodenal release at pH 5.5. In some embodiments, the composition comprises a powder of freeze-dried of the bacteria described herein which is deemed to have “Qualified Presumption of Safety” (QPS) status. In some embodiments, the composition is storage-stable at frozen or refrigerated temperature. As used herein, “stably stored” or “storage-stable” refer to a composition in which cells are able to withstand storage for extended periods of time (e.g., at least one month, or two, three, four, six, or twelve months or more) with a less than 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 15%, 10%, 5%, or 1% decrease in cell viability. 96 FH12512877.6 Attorney Docket No.: NEX-16225 In some embodiments using a culturing step, the agar or broth may contain nutrients that provide essential elements and specific factors that enable growth. An example would be a medium composed of 20 g / L glucose, 10 g / L yeast extract, 10 g / L soy peptone, 2 g / L citric acid, 1.5 g / L sodium phosphate monobasic, 100 mg / L ferric ammonium citrate, 80 mg / L magnesium sulfate, 10 mg / L hemin chloride, 2 mg / L calcium chloride, 1 mg / L menadione. Another example would be a medium composed of 10 g / L beef extract, 10 g / L peptone, 5 g / L sodium chloride, 5 g / L dextrose, 3 g / L yeast extract, 3 g / L sodium acetate, 1 g / L soluble starch, and 0.5 g / L L-cysteine HCl, at pH 6.8. A variety of microbiological media and variations are well known in the art (e.g., R.M. Atlas, Handbook of Microbiological Media (2010) CRC Press). Culture media can be added to the culture at the start, may be added during the culture, or may be intermittently / continuously flowed through the culture. The strains in the bacterial composition may be cultivated alone, as a subset of the microbial composition, or as an entire collection comprising the microbial composition. As an example, a first strain may be cultivated together with a second strain in a mixed continuous culture, at a dilution rate lower than the maximum growth rate of either cell to prevent the culture from washing out of the cultivation. The inoculated culture is incubated under favorable conditions for a time sufficient to build biomass. For microbial compositions for human use this is often at 37°C temperature, pH, and other parameter with values similar to the normal human niche. The environment may be actively controlled, passively controlled (e.g., via buffers), or allowed to drift. For example, for anaerobic bacterial compositions, an anoxic / reducing environment may be employed. This can be accomplished by addition of reducing agents such as cysteine to the broth, and / or stripping it of oxygen. As an example, a culture of a bacterial composition may be grown at 37°C, pH 7, in the medium above, pre-reduced with 1 g / L cysteine-HCl. When the culture has generated sufficient biomass, it may be preserved for banking. The organisms may be placed into a chemical milieu that protects from freezing (adding ‘cryoprotectants’), drying (‘lyoprotectants’), and / or osmotic shock (‘osmoprotectants’), dispensing into multiple (optionally identical) containers to create a uniform bank, and then treating the culture for preservation. Containers are generally impermeable and have closures that assure isolation from the environment. Cryopreservation treatment is accomplished by freezing a liquid at ultra-low temperatures (e.g., at or below -80°C). Dried preservation removes water from the culture by evaporation (in the case of spray drying or ‘cool drying’) or by sublimation (e.g., for freeze drying, spray freeze drying). Removal of water improves long-term microbial composition storage stability at temperatures elevated above cryogenic 97 FH12512877.6 Attorney Docket No.: NEX-16225 conditions. Microbial composition banking may be done by culturing and preserving the strains individually, or by mixing the strains together to create a combined bank. As an example of cryopreservation, a microbial composition culture may be harvested by centrifugation to pellet the cells from the culture medium, the supernatant decanted and replaced with fresh culture broth containing 15% glycerol. The culture can then be aliquoted into 1 mL cryotubes, sealed, and placed at -80°C for long-term viability retention. This procedure achieves acceptable viability upon recovery from frozen storage. Microbial production may be conducted using similar culture steps to banking, including medium composition and culture conditions described above. It may be conducted at larger scales of operation, especially for clinical development or commercial production. At larger scales, there may be several subcultivations of the microbial composition prior to the final cultivation. At the end of cultivation, the culture is harvested to enable further formulation into a dosage form for administration. This can involve concentration, removal of undesirable medium components, and / or introduction into a chemical milieu that preserves the microbial composition and renders it acceptable for administration via the chosen route. For example, a microbial composition may be cultivated to a concentration of 1010CFU / mL, then concentrated 20-fold by tangential flow microfiltration; the spent medium may be exchanged by diafiltering with a preservative medium consisting of 2% gelatin, 100 mM trehalose, and 10 mM sodium phosphate buffer. The suspension can then be freeze-dried to a powder and titrated. After drying, the powder may be blended to an appropriate potency, and mixed with other cultures and / or a filler such as microcrystalline cellulose for consistency and ease of handling, and the bacterial composition formulated as provided herein. In certain aspects, provided are bacterial compositions for administration in subjects. In some embodiments, the bacterial compositions are combined with additional active and / or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format. In some embodiments, the composition comprises at least one carbohydrate. A “carbohydrate” refers to a sugar or polymer of sugars. The terms “saccharide,” “polysaccharide,” “carbohydrate,” and “oligosaccharide” may be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule. Carbohydrates generally have the molecular formula CnH2nOn. A carbohydrate may be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide. The most basic carbohydrate is a monosaccharide, such as glucose, sucrose, 98 FH12512877.6 Attorney Docket No.: NEX-16225 galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two joined monosaccharides. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose. Typically, an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates may contain modified saccharide units such as 2’-deoxyribose wherein a hydroxyl group is removed, 2’-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N- acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2’-fluororibose, deoxyribose, and hexose). Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers. In some embodiments, the composition comprises at least one lipid. As used herein, a “lipid” includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans). In some embodiments the lipid comprises at least one fatty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1), margaric acid (17:0), heptadecenoic acid (17:1), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20:1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EPA), docosanoic acid (22:0), docosenoic acid (22:1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and tetracosanoic acid (24:0). In some embodiments the composition comprises at least one modified lipid, for example a lipid that has been modified by cooking. In some embodiments, the composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof. In some embodiments, the composition comprises at least one supplemental vitamin. The at least one vitamin can be fat-soluble or water-soluble vitamins. Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the 99 FH12512877.6 Attorney Docket No.: NEX-16225 vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin. In some embodiments, the composition comprises an excipient. Non-limiting examples of suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent. In some embodiments, the excipient is a buffering agent. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate. In some embodiments, the excipient comprises a preservative. Non-limiting examples of suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol. In some embodiments, the composition comprises a binder as an excipient. Non- limiting examples of suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof. In some embodiments, the composition comprises a lubricant as an excipient. Non- limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil. In some embodiments, the composition comprises a dispersion enhancer as an excipient. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants. In some embodiments, the compositions of the present invention are combined with a carrier (e.g., a pharmaceutically acceptable carrier) which is physiologically compatible with the gastrointestinal tissue of the subject(s) to which it is administered. Carriers can be comprised of solid-based, dry materials for formulation into tablet, capsule or powdered form; or the carrier can be comprised of liquid or gel-based materials for formulations into liquid or gel forms. The specific type of carrier, as well as the final formulation depends, in 100 FH12512877.6 Attorney Docket No.: NEX-16225 part, upon the selected route(s) of administration. The therapeutic composition of the present invention may also include a variety of carriers and / or binders. In some embodiments, the carrier is micro-crystalline cellulose (MCC) added in an amount sufficient to complete the one gram dosage total weight. Carriers can be solid-based dry materials for formulations in tablet, capsule or powdered form, and can be liquid or gel-based materials for formulations in liquid or gel forms, which forms depend, in part, upon the routes of administration. Typical carriers for dry formulations include, but are not limited to: trehalose, malto-dextrin, rice flour, microcrystalline cellulose (MCC) magnesium sterate, inositol, FOS, GOS, dextrose, sucrose, and like carriers. Suitable liquid or gel-based carriers include but are not limited to: water and physiological salt solutions; urea; alcohols and derivatives (e.g., methanol, ethanol, propanol, butanol); glycols (e.g., ethylene glycol, propylene glycol, and the like). Preferably, water-based carriers possess a neutral pH value (i.e., pH 7.0). Other carriers or agents for administering the compositions described herein are known in the art, e.g., in U.S. Patent No. 6,461,607. In some embodiments, the composition comprises a disintegrant as an excipient. In some embodiments, the disintegrant is a non-effervescent disintegrant. Non-limiting examples of suitable non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth. In some embodiments the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid. In some embodiments, the bacterial formulation comprises an enteric coating or micro encapsulation. In certain embodiments, the enteric coating or micro encapsulation improves targeting to a desired region of the gastrointestinal tract. For example, in certain embodiments, the bacterial composition comprises an enteric coating and / or microcapsules that dissolves at a pH associated with a particular region of the gastrointestinal tract. In some embodiments, the enteric coating and / or microcapsules dissolve at a pH of about 5.5 – 6.2 to release in the duodenum, at a pH value of about 7.2 – 7.5 to release in the ileum, and / or at a pH value of about 5.6 – 6.2 to release in the colon. Exemplary enteric coatings and microcapsules are described, for example, in U.S. Pat. Pub. No.2016 / 0022592, which is hereby incorporated by reference in its entirety. 101 FH12512877.6 Attorney Docket No.: NEX-16225 In some embodiments, the composition is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed. Specific examples of the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, capsules, liquids, pastes, and jellies. The composition may be a fermented food product, such as, but not limited to, a fermented milk product. Non-limiting examples of fermented food products include kombucha, sauerkraut, pickles, miso, tempeh, natto, kimchi, raw cheese, and yogurt. The composition may also be a food additive, such as, but not limited to, an acidulent (e.g., vinegar). Food additives can be divided into several groups based on their effects. Non-limiting examples of food additives include acidulents (e.g., vinegar, citric acid, tartaric acid, malic acid, fumaric acid, and lactic acid), acidity regulators, anticaking agents, antifoaming agents, foaming agents, antioxidants (e.g., vitamin C), bulking agents (e.g., starch), food coloring, fortifying agents, color retention agents, emulsifiers, flavors and flavor enhancers (e.g., monosodium glutamate), flour treatment agents, glazing agents, humectants, tracer gas, preservatives, stabilizers, sweeteners, and thickeners. In certain embodiments, the bacteria disclosed herein are administered in conjunction with a prebiotic to the subject. Prebiotics are carbohydrates which are generally indigestible by a host animal and are selectively fermented or metabolized by bacteria. Prebiotics may be short-chain carbohydrates (e.g., oligosaccharides) and / or simple sugars (e.g., mono- and di- saccharides) and / or mucins (heavily glycosylated proteins) that alter the composition or metabolism of a microbiome in the host. The short chain carbohydrates are also referred to as oligosaccharides, and usually contain from 2 or 3 and up to 8, 9, 10, 15 or more sugar 102 FH12512877.6 Attorney Docket No.: NEX-16225 moieties. When prebiotics are introduced to a host, the prebiotics affect the bacteria within the host and do not directly affect the host. In certain aspects, a prebiotic composition can selectively stimulate the growth and / or activity of one of a limited number of bacteria in a host. Prebiotics include oligosaccharides such as fructooligosaccharides (FOS) (including inulin), galactooligosaccharides (GOS), trans-galactooligosaccharides, xylooligosaccharides (XOS), chitooligosaccharides (COS), soy oligosaccharides (e.g., stachyose and raffinose) gentiooligosaccharides, isomaltooligosaccharides, mannooligosaccharides, maltooligosaccharides and mannanoligosaccharides. Oligosaccharides are not necessarily single components, and can be mixtures containing oligosaccharides with different degrees of oligomerization, sometimes including the parent disaccharide and the monomeric sugars. Various types of oligosaccharides are found as natural components in many common foods, including fruits, vegetables, milk, and honey. Specific examples of oligosaccharides are lactulose, lactosucrose, palatinose, glycosyl sucrose, guar gum, gum Arabic, tagalose, amylose, amylopectin, pectin, xylan, and cyclodextrins. Prebiotics may also be purified or chemically or enzymatically synthesized. Therapeutic Methods In certain aspects, provided herein are methods of treating a disease associated with increased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism described herein, wherein the microorganism consumes H2S. The disease associated with increased H2S levels may be a neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, inflammatory bowel disease (IBD), an ulcer, colorectal cancer, mental retardation, Down Syndrome, intestinal pain, H2S poisoning, an inflammatory disease, or diabetes mellitus. In certain aspects, provided herein are methods of treating a disease associated with decreased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism described herein, wherein the microorganism produces H2S. The disease associated with decreased H2S levels may be a cardiovascular disease, hypertension, a kidney disease, or a retinal disease. In certain aspects, provided herein are methods of treating a disease associated with changes in H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism described herein. The disease associated with 103 FH12512877.6 Attorney Docket No.: NEX-16225 changes in H2S levels may be neurodegenerative disease (Tripathi SJ, Chakraborty S, Miller E, Pieper AA, Paul BD. Hydrogen sulfide signalling in neurodegenerative diseases. Br J Pharmacol), a myocardial injury (Elrod JW, Calvert JW, Morrison J, et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function), an ophthalmic disease (Li P, Liu H, Shi X, Prokosch V. Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases. Molecules.2021;26(9):2411), a gastrointestinal disorder (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms.2015;3(4):866- 889), inflammatory bowel disease (IBD) (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms.2015;3(4):866-889), irritable bowel syndrome (IBS) (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms.2015;3(4):866-889), an ulcer (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms. 2015;3(4):866-889), colorectal cancer (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms.2015;3(4):866-889), mental retardation (Szabo C. The re-emerging pathophysiological role of the cystathionine-β-synthase - hydrogen sulfide system in Down syndrome. FEBS J.2020;287(15):3150-3160), Down Syndrome (Szabo C. The re-emerging pathophysiological role of the cystathionine-β- synthase - hydrogen sulfide system in Down syndrome. FEBS J.2020;287(15):3150-3160), intestinal pain (Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms.2015;3(4):866-889), H2S poisoning (Sawaya A, Regina AC, Menezes RG. Hydrogen Sulfide Toxicity. [Updated 2024 May 2]. In: StatPearls [Internet]), an inflammatory disease (Bhatia M, Gaddam RR. Hydrogen Sulfide in Inflammation: A Novel Mediator and Therapeutic Target. Antioxid Redox Signal. 2021;34(17):1368-1377), a cardiometabolic disease (Kolluru, G.K., Shackelford, R.E., Shen, X. et al. Sulfide regulation of cardiovascular function in health and disease. Nat Rev Cardiol 20, 109–125 (2023), Ethylmalonic encephalopathy (Tiranti V, Zeviani M. Altered sulfide (H(2)S) metabolism in ethylmalonic encephalopathy. Cold Spring Harb Perspect Biol. 2013;5(1):a011437), liver fibrosis (Wu DD, Wang DY, Li HM, Guo JC, Duan SF, Ji XY. Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease. Oxid Med Cell Longev.2019;2019:3831713), liver ischemia‒reperfusion injury (Wu DD, Wang DY, Li HM, Guo JC, Duan SF, Ji XY. Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease. Oxid Med Cell Longev.2019;2019:3831713), hepatocellular carcinoma (Wu DD, Wang DY, Li HM, Guo JC, Duan SF, Ji XY. Hydrogen Sulfide as a Novel Regulatory Factor 104 FH12512877.6 Attorney Docket No.: NEX-16225 in Liver Health and Disease. Oxid Med Cell Longev.2019;2019:3831713), hepatotoxicity (Wu DD, Wang DY, Li HM, Guo JC, Duan SF, Ji XY. Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease. Oxid Med Cell Longev.2019;2019:3831713), acute liver failure (Wu DD, Wang DY, Li HM, Guo JC, Duan SF, Ji XY. Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease. Oxid Med Cell Longev. 2019;2019:3831713), osteoporosis (Grassi F, Tyagi AM, Calvert JW, et al. Hydrogen Sulfide Is a Novel Regulator of Bone Formation Implicated in the Bone Loss Induced by Estrogen Deficiency. J Bone Miner Res.2016;31(5):949-963), central nervous diseases like Alzheimer's disease (Sharif AH, Iqbal M, Manhoosh B, et al. Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges. Neurochem Res. 2023;48(7):1981-1996), Parkinson's disease (Sharif AH, Iqbal M, Manhoosh B, et al. Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges. Neurochem Res.2023;48(7):1981-1996), Huntington's disease (Sharif AH, Iqbal M, Manhoosh B, et al. Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges. Neurochem Res.2023;48(7):1981-1996), and ischemic stroke (Sharif AH, Iqbal M, Manhoosh B, et al. Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges. Neurochem Res.2023;48(7):1981- 1996), skin diseases such as burn (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res. 2020;27:11-17), diabetic skin wound (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res. 2020;27:11-17), psoriasis (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res.2020;27:11-17), systemic sclerosis (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res.2020;27:11-17), melanoma (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res.2020;27:11-17), pruritus (Xu M, Zhang L, Song S, et al. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res.2020;27:11-17). In one aspect the present disclosure provides a method of reducing H2S levels in environmental water or wastewater, comprising administering thereof an effective amount of the engineered microorganism described herein. The method is used for the environmental degradation of H2S. For example, using the same engineered microbes described herein for degrading H2S from wastewater plants or source waters used in drilling. 105 FH12512877.6 Attorney Docket No.: NEX-16225 Administration In certain aspects, provided herein is a method of delivering a pharmaceutical composition described herein to a subject. In some embodiments of the methods provided herein, the pharmaceutical composition is administered in conjunction with the administration of an additional therapeutic. In some embodiments, the pharmaceutical composition comprises the engineered microorganism co-formulated with the additional therapeutic. In some embodiments, the pharmaceutical composition is co-administered with the additional therapeutic. In some embodiments, the additional therapeutic is administered to the subject before administration of the pharmaceutical composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours before, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days before). In some embodiments, the additional therapeutic is administered to the subject after administration of the pharmaceutical composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours after, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days after). In some embodiments the same mode of delivery are used to deliver both the pharmaceutical composition and the additional therapeutic. In some embodiments different modes of delivery are used to administer the pharmaceutical composition and the additional therapeutic. For example, in some embodiments the pharmaceutical composition is administered orally while the additional therapeutic is administered via injection (e.g., an intravenous, intramuscular and / or intratumoral injection). The dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the particular microorganism to be administered, duration and route of administration, the kind and stage of the disease, for example, tumor size, and other compounds such as drugs being administered concurrently or near-concurrently. In addition to the above factors, such levels can be affected by the infectivity of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art. In the present methods, appropriate minimum dosage levels of microorganisms can be levels sufficient for the microorganism to survive, grow and replicate. The dose of the pharmaceutical compositions described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, 106 FH12512877.6 Attorney Docket No.: NEX-16225 the degree or stage of a target disease, and the like. For example, the general effective dose of the agents may range between 0.01 mg / kg body weight / day and 1000 mg / kg body weight / day, between 0.1 mg / kg body weight / day and 1000 mg / kg body weight / day, 0.5 mg / kg body weight / day and 500 mg / kg body weight / day, 1 mg / kg body weight / day and 100 mg / kg body weight / day, or between 5 mg / kg body weight / day and 50 mg / kg body weight / day. The effective dose may be 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, or 1000 mg / kg body weight / day or more, but the dose is not limited thereto. In some embodiments, the dose administered to a subject is sufficient to prevent disease (e.g., autoimmune disease, inflammatory disease, metabolic disease, cancer), delay its onset, or slow or stop its progression. One skilled in the art will recognize that dosage will depend upon a variety of factors including the strength of the particular compound employed, as well as the age, species, condition, and body weight of the subject. The size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect. Suitable doses and dosage regimens can be determined by conventional range-finding techniques known to those of ordinary skill in the art. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. An effective dosage and treatment protocol can be determined by routine and conventional means, starting e.g., with a low dose in laboratory animals and then increasing the dosage while monitoring the effects, and systematically varying the dosage regimen as well. Animal studies are commonly used to determine the maximal tolerable dose ("MTD") of bioactive agent per kilogram weight. Those skilled in the art regularly extrapolate doses for efficacy, while avoiding toxicity, in other species, including humans. In accordance with the above, in therapeutic applications, the dosages of the active agents used in accordance with the invention vary depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage. Generally, the dose should be sufficient to result in slowing, and preferably regressing, the growth of the tumors and most preferably causing complete regression of the cancer. 107 FH12512877.6 Attorney Docket No.: NEX-16225 Separate administrations can include any number of two or more administrations, including two, three, four, five or six administrations. One skilled in the art can readily determine the number of administrations to perform or the desirability of performing one or more additional administrations according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein. Accordingly, the methods provided herein include methods of providing to the subject one or more administrations of an pharmaceutical composition, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results. The time period between administrations can be any of a variety of time periods. The time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response and / or the time period for a subject to clear the MP from normal tissue. In one example, the time period can be a function of the time period for a subject to mount an immune response; for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be less than the time period for a subject to mount an immune response, such as less than about one week, less than about ten days, less than about two weeks, or less than about a month. In another example, the time period can be a function of the time period for a subject to clear the MP from normal tissue; for example, the time period can be more than the time period for a subject to clear the MP from normal tissue, such as more than about a day, more than about two days, more than about three days, more than about five days, or more than about a week. In some embodiments, the delivery of an additional therapeutic in combination with the pharmaceutical composition described herein reduces the adverse effects and / or improves the efficacy of the additional therapeutic. The effective dose of an additional therapeutic described herein is the amount of the therapeutic agent that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, with the least toxicity to the patient. The effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular 108 FH12512877.6 Attorney Docket No.: NEX-16225 compositions administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. In general, an effective dose of an additional therapy will be the amount of the therapeutic agent which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. The toxicity of an additional therapy is the level of adverse effects experienced by the subject during and following treatment. Adverse events associated with additional therapy toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylasix, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery disease, cataracts, central neurotoxicity, cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspepsia, dyspnea, edema, electrolyte imbalance, esophagitis, fatigue, loss of fertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytopenia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, hearing loss, heart failure, heart palpitations, heartburn, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylasemia, hypercalcemia, hyperchloremia, hyperglycemia, hyperkalemia, hyperlipasemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, impotence, infection, injection site reactions, insomnia, iron deficiency, itching, joint pain, kidney failure, leukopenia, liver dysfunction, memory loss, menopause, mouth sores, mucositis, muscle pain, myalgias, myelosuppression, myocarditis, neutropenic fever, nausea, nephrotoxicity, neutropenia, nosebleeds, numbness, ototoxicity, pain, palmar- plantar erythrodysesthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonia, pneumonitis, proteinuria, pulmonary embolus, pulmonary fibrosis, pulmonary toxicity, rash, rapid heart beat, rectal bleeding, restlessness, rhinitis, seizures, shortness of breath, sinusitis, thrombocytopenia, tinnitus, urinary tract 109 FH12512877.6 Attorney Docket No.: NEX-16225 infection, vaginal bleeding, vaginal dryness, vertigo, water retention, weakness, weight loss, weight gain, and xerostomia. In general, toxicity is acceptable if the benefits to the subject achieved through the therapy outweigh the adverse events experienced by the subject due to the therapy. EXAMPLES Example 1: Methods for Modulating Hydrogen Sulfide Concentrations in the Human Intestine We have shown our ability to engineer sulfide production in E. coli. For sulfide production (steps 5-6 in Fig.2), we knocked out the native E. coli gene, decR, which reduces native L-cysteine derived H2S production by 80% giving us greater control. Using heterologous and native desulfidases, different strength promoters, and transporter engineering, we generated a library of strains capable of titrating H2S across the gut physiological range (300-3,400 μM). For testing their ability to produce sulfide in a more physiologically relevant model, we deployed these microbes in a human gut-on-chip system and showed they perform as expected in a simulated intestinal environment. We showed dose-dependent effects of sulfide on host physiology which supports the rationale for controlling sulfide levels in the human gut. Recently we have engineered a two-step synthetic pathway for sulfide sequestration in which H2S is converted to L-cysteine and then glutathione, leading to its accumulation intracellularly (Figs.4A and 4B). We next engineered a pathway to break down extracellular glutathione into H2S (Figure 4 C). Convert intracellular glutathione to H2S directly is tested. We adapted an H2S sensor from Bacillus licheniformis to control luminal sulfide levels within a therapeutic window (Fig.3). The nreB / C system from B. licheniformis works by directly sensing H2S and phosphorylating a transcription factor, which we use to drive expression of the production or consumption pathways. For example, if the microbe senses intestinal sulfide below the engineered set-point, it turns on the sulfide production pathway. Conversely, if intestinal sulfide levels are too high, the consumption pathway will be activated. Unlike the CstR and SqrR sulfide sensing systems, the nreB / C system has not yet been used for sensing H2S. Further, the CstR and SqrR systems rely on sulfide oxidation followed by sensing of hydrogen polysulfides, whereas the nreB / C sensor directly senses H2S. 110 FH12512877.6 Attorney Docket No.: NEX-16225 Example 2: Engineered bacteria titrate hydrogen sulfide and induce concentration dependent effects on host in a gut microphysiological system Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non- representative model systems. Here, we engineered E. coli to titrate H2S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H2S gas tension and enable visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a novel platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal and in vitro models. Methods Strain development and growth curves The decR, sseA, and malY genes were knocked out of E. coli MG1655 using the λ- Red recombination and CRISPR Cas9 systems. The pCas (Addgene plasmid #62225) and pTargetF (Addgene plasmid #62226) plasmids were gifts from Sheng Yang. A custom N20 sequence was added to pTargetF via PCR to target each gene of interest directly. pCas and pTargetF were transformed and cured according to the protocol. Colonies were picked, and knockouts were verified with PCR and Sanger sequencing (Genewiz from Azenta Life Sciences). The strains were grown overnight in M9 minimal media (4 g / L glucose, 1 g / L casamino acids (cat.502 no 2240, VWR), and 1 mg / L thiamine (cat. no T4625, Sigma- Aldrich)) and diluted to an OD600 of 0.01 with M9 minimal media or M9 minimal media with 5 mM cysteine (cat no.30129, Millipore Sigma). The strains were added to 96 well plates (cover on) and were grown for 16 hours at 37C in a plate reader (SpectraMax i3, Molecular Devices) in technical triplicates or quadruplicates. The plate was shaken at medium speed and OD600 reads were taken every ten minutes. E. coli genes (decR, yhaM, yhaO) were cloned from E. coli MG1655 gDNA (cat no. T3010, New England Biolabs Inc.) via PCR. The cdl gene (from F. nucleatum) was codon optimized for E. coli and synthesized (Integrated DNA Technologies). Gibson assembly (cat no. E2621, New England Biolabs Inc.) was used to assemble backbones and genes of interest. 111 FH12512877.6 Attorney Docket No.: NEX-16225 Once assembled, plasmids were chemically transformed into DH5-alpha cells (cat no. C2987, New England Biolabs Inc.) and plated on agar plates containing appropriate antibiotics. Colonies were picked and were sequence verified with PCR and Sanger sequencing. Once verified, plasmids were mini-prepped (cat no. D4211, Zymo Research) and transformed into the chemically competent MG1655-ΔdecR. Hungate tube experiments Cultures were grown overnight in M9 minimal media and diluted 1:25 with M9 minimal media in shake flasks. For strains bearing plasmids with the lacUV5 (variable induction), T7 (100 μM IPTG induction), and pBAD (10 mM L-arabinose induction) promoters, they were induced at OD6000.6 for two hours. Cultures were centrifuged and resuspended to OD6000.4 with PBS++ (non-growth experiments) or M9 minimal media (growth experiments). Negative controls had no cysteine.5 mL of culture were added to sterile Hungate tubes and placed in a shaking incubator at 37C. Samples were taken with sterile needles at hours two and four while maintaining a closed and sterile system. H2S production was quantified with the methylene blue assay. H2S detection by methylene blue assay The protocol was adapted and adjusted to detect H2S in liquid samples.200 μL of the experimental sample was added to 615 μL zinc acetate mixture (600 μL of 1% w / v zinc acetate dihydrate with 15 uL 3 M NaOH) and vortexed. After 5-10 minutes of incubating at room temperature, 150 μL of 0.1% n-n-dimethylethylenediamine (cat no. D157805, Millipore Sigma) in 5 M hydrochloric acid was added, followed by 150 μL of 23 mM ferric chloride (cat no.12321, Sigma Aldrich) in 1 M hydrochloric acid. Samples were centrifuged at 16,000 RCF for 2 minutes.200 μL of supernatant were plated in a transparent 96-well plate and were quantified using absorbance (670 nm) (SpectraMax i3, Molecular Devices). For Hungate tube experiments, 200 μL samples were taken from Hungate tubes with a sterile syringe needle while maintaining a sterile closed system. For GMPS experiments, apical and basal effluent tubing was fed into collection tubes containing 2.2 mL of zinc acetate mixture to trap H2S over the sampling period (four hours at 180 μL / min). After four hours, effluent collection tubes were vortexed, and 815 μL of effluent / zinc acetate mixture was taken to be used for subsequent steps. Standard curves were made by dissolving Na2S in 0.1 M NaOH and serially diluted in PBS++ or DMEM. The zinc acetate mixture was immediately added, tubes were vortexed, and samples sat at room temperature for at least 5 minutes. Mixtures were used for 112 FH12512877.6 Attorney Docket No.: NEX-16225 subsequent steps, and methylene blue was measured as described. Sample standard curves of PBS++ and DMEM are provided in Fig.14. GMPS fabrication The GMPS device used in this study is a derivative of previous work from our lab. The fabrication used poly(methyl methacrylate) (PMMA) sheets, PET membranes, double- sided adhesive tape, and a laser cutter. Each layer of the chip was designed with computer- aided drafting (CAD, Autodesk Inventor) and was laser cut (Epilog Zing 16, Epilog Laser). The 3 / 16” PMMA (PMMA, McMaster-Carr) contained six laser cut holes, two for inlet flow, two for outlet flow, and two for access to apical and basal channels (referred to as ‘seed ports’), which were tapped to create threading for Luer lock fittings. This piece served as the top layer of the device. The second layer was a sheet of 1 / 16” PMMA (PMMA, McMaster- Carr) inserted between two pieces of 50 μm thick double-sided adhesive tape (966 Adhesive Transfer Tape, 3M), which served as the ceiling of the apical channel. All six circular inlets and outlets were laser-cut to match the through-holes in the top layer. The third layer was a PET membrane with 0.4 μm diameter pores (ipCELLCULTURE Track Etched Membrane, it4ip S.A.) that sat between the second and fourth layers, creating a cell culture surface for the apical channel. Circular inlets and outlets were laser-cut to match the through-holes in the fourth layer. A sheet of 1 / 16” PMMA inserted between two pieces of 50 μm thick double- sided adhesive tape served as the fourth layer and the ceiling of the basal channel. Three circular inlets and outlets were laser cut to match the through-holes in the top two layers. The fifth layer was a no.1 glass coverslip that sealed the basal channel. Using a custom device, the layers were pressed together while maintaining the alignment of the holes and channels. After assembly, the chips were pressed and stored under vacuum at 50C for two days to rid gas bubbles in the device. Male Leur lock fittings (cat no 40064, QOSINA) with Viton O-Rings 5 / 32" 574 ID 9 / 32" OD (cat no.1284N107, McMaster-Carr) were fitted to all six threaded holes in the 3 / 16” layer. Female Leur locks to barb connectors were fitted to the two inlets and outlets to connect Soft PVC Clear Tubing, 1 / 16" ID, 1 / 8" OD (McMaster-Carr). The apical port served as a seed port for Caco-2 and bacteria. Otherwise, throughout the experiment, the two seed ports were capped and sealed. The PVC tubing was connected to a syringe pump (NE-1600 Six Channel Programmable Syringe Pump, New Era Pump Systems Inc.), perfusing culture medium through the chip. Details of the GMPS can be found in a schematic in Figure 5. The fluidic shear stress (τ, dyne / cm) was calculated by the approximation of flow between two parallel plates 113 FH12512877.6 Attorney Docket No.: NEX-16225 τ=6μQ ^^ℎ where μ is the dynamic viscosity of the apical fluid [0.0097 g / cm-s], Q is the volumetric flow rate [0.00005 cm / sec], w is the width of the apical channel [0.1 cm], and h is the height of the apical channel [0.0196 cm]. Caco-2 cell culture in GMPS Caco-2 cells were obtained from the American Type Culture Collection (ATCC) and cultured in Dulbecco’s Modified Eagle Medium (DMEM, cat no. MT10013CV, Corning) supplemented with 10% fetal bovine serum (FBS, cat no.10437028, ThermoFisher) and 100 U / mL penicillin−streptomycin (cat no.15140122, ThermoFisher). Microfluidic chips were removed from the vacuum chamber and UV sterilized (300 mJ / cm) for 10 minutes (Spectrolinker XL- 1000, Spectronics Corporation) on each side. Chips were then treated with oxygen plasma (Expanded Plasma Cleaner PDC-001, Harrick Plasma) for 1 minute. Fittings and tubing were sterilized by autoclaving. The chips, fittings, tubing, and syringe pump were assembled in a biosafety cabinet using an aseptic technique. The apical channel was coated in a 400 μg / mL solution of rat tail type I collagen (cat no. 354249, Corning), after which the chips were placed in a humidified incubator at 37C and 5% CO2for one hour. After this time, the culture medium was perfused through the chip in preparation for seeding Caco-2. Caco-2 cells were harvested from flasks and concentrated to 5,000,000 cells / mL.200 μL of Caco-2 cells were manually injected into the chip via the apical seed port. The chip set-up was placed in a humidified incubator at 37C and 5% CO2without flow for two hours to allow cell adhesion. After two hours, the apical and basal flow was initiated at 3 μL / minute (shear stress 0.076 dyne / cm). Effluent media was collected in waste collection tubes. Chips were under flow for seven days. On the seventh day, apical media was swapped for sterile PBS++ (pH 7.4) with 25 mM Lucifer Yellow (cat no. L453, Thermo Fisher). PBS++ was made of 1 L of DPBS, no calcium, no magnesium (cat no. 14190144, Thermo Fisher), 2.4 g / L HEPES (cat no. BP310-1, Fisher Scientific), 100 g / L anhydrous calcium chloride (cat no.349615000, Thermo Fisher), and 48.4 g / L pure magnesium chloride (cat no.223210010, Thermo Fisher). The basal media was swapped with antibiotic-free DMEM with 10% FBS in preparation for the inoculation of engineered strains. The media was allowed to perfuse through the chip overnight to clear residual antibiotics. For this study, Caco-2 cells were between passage numbers 25 and 47. Inoculating bacteria in GMPS One to two hours before inoculation, the GMPS set-up was moved to the biosafety cabinet, and all apical and basal syringes were swapped to prime the chip. Before priming the 114 FH12512877.6 Attorney Docket No.: NEX-16225 chip, the media was filter sterilized. The basal media was swapped with antibiotic-free DMEM with 10% FBS in preparation for the inoculation of engineered strains. The following table describes the contents of each apical syringe used for each experiment. The syringes were flowed at 30 μL / min for ten minutes to clear any air bubbles introduced during handling. After ten minutes, the flow was restored to 3 μL / min. Bacterial cultures were grown overnight in M9 minimal media and diluted 1:25 with M9 minimal media in shake flasks. For strains bearing plasmids with the lacUV5 (variable induction 0-250 μM IPTG), T7 (100 μM IPTG induction), and pBAD (10 mM L-arabinose 115 FH12512877.6 Attorney Docket No.: NEX-16225 induction) promoters, they were induced at OD6000.6 for two hours. Cultures were centrifuged and resuspended to OD6000.4 with their respective apical channel media. Sodium sulfide nonahydrate (Na2S) (cat no.208043, Sigma Aldrich) was used for exogenous sulfide. DSS (cat no. AC433240050 Fisher Scientific) was dissolved in PBS++ to 3% w / v. Next, the GMPS set-up was moved to the biosafety cabinet, and flow was paused.200 μL of bacteria were injected into the apical seed port at an OD600 of 0.4 using a syringe pump (100 μL / min). Once inoculated, the chip set-up was moved back into the humidified incubator at 37C 5% CO2, and flow was resumed immediately at 3 μL / min. Throughout this study, inoculation is defined as hour zero. Gut permeability analysis (Papp calculations) 25 mM Lucifer Yellow was added to apical syringes the night before inoculating the chips. Four hours prior to inoculation, GMPS basal effluent was collected for two hours to establish a baseline Papp. Additionally, effluent samples were collected at hours 18 and 42 of the experiment. Samples were quantified using a DMEM standard curve using a fluorescence plate reader (SpectraMax i3, Molecular Devices) (ex: 485 nm, em: 535 nm). The CO2in the incubator drives down the pH of DMEM, affecting the fluorescent properties at these excitation / emission values. To control for CO2-induced pH changes in the DMEM, an additional DMEM syringe was incubated overnight and used to make the standard curve. Apparent permeability (Papp, cm / sec) was calculated with the following equation ^^ ^^ ^^ ^^=Cb^^ ^^ ^^ ^^ ^^ / ^^ ^^ ^^ ^^c ^^ ^^ ^^. ^^. where Cbasal is the concentration of Lucifer Yellow detected in the basal channel as determined by the standard curve [μM], F is the flow rate [0.00005 cm3 / sec], Capical is the concentration of Lucifer Yellow in the apical channel [25 μM], and S.A. is the surface area of the Caco-2 monolayer [0.1341 cm2]. CFU analysis Apical and basal effluent was collected at hours -4, 18, and 42. Apical samples were serially diluted 1,000-fold or 10,000-fold, and 50 μL were plated on LB agar plates containing appropriate antibiotics or antibiotic-free plates for control chip samples. For basal samples, 50 μL of basal effluent was directly plated. Agar plates were incubated overnight at 37C and counted the following day. For apical samples, the CFU count was multiplied by a factor of 20,000 (for 1,000-fold diluted samples) or 200,000 (for 10,000-fold diluted samples) to get units of CFU / mL. In bacteria-free chips, apical and basal effluent were plated on LB agar plates, and no colonies were detected. 116 FH12512877.6 Attorney Docket No.: NEX-16225 Metabolite quantification with HPLC Apical and basal effluent samples were collected at hours -4, 18, and 42 and was immediately stored at -80C. For glucose and acetate analysis, samples were thawed, centrifuged, and the supernatant was loaded into HPLC tubes. An Agilent 1260 HPLC Infinity II system was used with an isocratic flow of 14 mM sulfuric acid at 0.6 mL / min.10 μL of the sample were injected into an Aminex HPX 87H ion (300x7.8 mm) C18 reversed phase column (cat no.1250140, BioRad) at 60C fitted with a Micro-Guard Cation H cartridge (cat no.1250129, Bio-Rad). Compounds were identified with a refractive index detector (1260 Infinity II Refractive Index Detector, Agilent) at 50C. Calibration curves of the pure compounds were used to identify and quantify compounds in experimental samples. The protocol was adapted and adjusted from the previous work. For detecting thiosulfate, samples were thawed, centrifuged, and the supernatant was used for monobromobimane (mBBr) derivatization (cat no.69898, Millipore Sigma). To derivatize 61 samples, 5 mM mBBr was dissolved in 200 mM Tris-HCl.10 μL of supernatant were added to 90 μL mBBr solution and incubated at room temperature for one hour, and samples were covered in foil. After one hour, 30 μL of 1M hydrochloric acid was added to terminate the reaction. Samples were centrifuged, and the supernatant was placed in HPLC tubes.5 μL of the sample were injected into a C18 reversed phase column (InfinityLab Poroshell 120 EC-C182.7 μm 3x100 mm, Agilent) at 40C and detected with an HPLC fluorescence detector (1260 Infinity II Fluorescence Detector, Agilent) at an excitation / emission spectra of 384 / 478 nm. The flow rate through the column was 0.5 mL / min, and a gradient elution was applied to separate thiols: 0-2 min, 0% B; 2-8 min, 46% B; 8-9 min, 64% B; 9-13 min, 100% B; 13-14 min, 0% B; 14-15 min, 0% B. Solvent A was 10% methanol and 0.25% glacial acetic acid, adjusted to pH 3.9. Solvent B was 90% methanol and 0.25% glacial acetic acid, adjusted to pH 3.9. The protocol was adapted and modified from previously described protocols. RT-qPCR analysis After two days of co-culture, the flow was stopped, and the GMPS set-up was removed from the incubator. Via the seed port, PBS++ was used to wash the apical channel, and 300 μL RNA lysis buffer (cat no. T2010, New England Biolabs Inc.) was applied to the channel and vigorously pipetted. RNA was purified following the manufacturer’s protocol (cat no. T2010, New England Biolabs Inc.). Oligo(dT)12-18 (cat no.18418012, Thermo Fisher) was used to reverse transcribe Caco-2 RNA (C1000 Touch Thermal Cycler, BioRad). The resulting cDNA was cleaned and concentrated (cat no. D40144, Zymo Research) and 1 117 FH12512877.6 Attorney Docket No.: NEX-16225 μL was used for qPCR. A SYBR Green-based qPCR master mix (cat no. M3003, New England Biolabs Inc.) and primers were used to amplify genes of interest (C1000 Thermal Cycler with CFX96 Real-Time System, BioRad). Primers were made with NCBI Primer Blast. The target gene, GADD45a, was normalized to GAPDH. Relative expression differences were calculated using the delta-delta Ct method. Immunofluorescent imaging in GMPS Images of tight junction formation were assessed using fluorescence microscopy. Monolayers were fixed by flowing 4% formaldehyde (v / v in 2.5% Goat Serum) at 9 μL / min for 30 minutes, 0.1% TritonX (v / v in 2.5% Goat Serum) at 9 μL / min for 20 minutes, and 2.5% goat serum for 30 minutes at room temperature. Chips were covered in foil and placed in the fridge (4C) overnight. The basal channel was flushed with PBS. Flow rates were kept below 10 μL / min in the apical channel to prevent high shear stress and monolayer disruption. The following day, 1:200 ZO-1 conjugated antibody (cat no. MA3-39100-A647, Thermo Fisher) and 1:10,000 Hoechst (cat no.62249, Thermo Fisher) were mixed in 2.5% goat serum and flowed at 6 μL / min for one hour. After one hour, the flow was paused, and the system sat static for one hour. Afterward, the monolayers were washed with DPBS for three hours at 4 μL / min. The GMPS was imaged with a confocal microscope (Zeiss LSM 880 NLO) using the DAPI and Alexa Fluor 647 filters. For live staining, T7-yhaM-RFP + BAD-yhaO was inoculated on the chip.1:2,000 Hoechst was added to apical and basal channels and flowed on the chip at 3 μL / min for three hours. Adding a higher concentration of Hoechst to apical and basal channels enhanced the signal, which may be attributed to the sizeable microbial population in the apical channel disrupting the mass transport of Hoechst to the Caco-2 nuclei. Before imaging, the basal channel was flushed with PBS. Next, the GMPS was imaged with confocal microscopy using the DAPI and mRFP-1.2 filters. A live video of the co-culture was captured using an inverted fluorescence microscope (Zeiss Axio Observer Z1). To do this, the GMPS was kept in an incubated microscope set up (37C and 5% CO2), and normal experimental conditions were maintained including perfusion through the chip. Images were captured overnight and assembled in a movie using Zen software (Zeiss) and Adobe Premier Pro. Image processing was done in Zen software (Zeiss). Gaussian smoothing was used for all images. Statistical analysis A one-way ANOVA or two-way ANOVA followed by post hoc Tukey-Kramer analysis were used to determine statistical significance (*p < 0.05). Bar graphs represent the 118 FH12512877.6 Attorney Docket No.: NEX-16225 average value from independent experiments, and dots represent the result from each independent experiment. Error bars represent the ± standard deviation. GraphPad Prism was used to carry out the analysis. Graphs were formatted in Adobe Illustrator. For each independent experiment, bacterial cultures were grown from cryostock, and Caco-2 cells were harvested from flasks. Independent experiments were performed on dif...

Claims

Attorney Docket No.: NEX-16225 We claim:

1. An engineered microorganism, comprising: a first gene encoding a serine acetyltransferase; and a second gene encoding a cysteine synthase A.

2. The engineered microorganism of claim 1, wherein the serine acetyltransferase has reduced L-cysteine feedback inhibition as compared to a wild-type serine acetyltransferase from the same bacterial subtype under the same conditions.

3. The engineered microorganism of claim 1, wherein the serine acetyltransferase is mutated at positions 167 and / or 256.

4. The engineered microorganism of claim 1 or 2, wherein the serine acetyltransferase comprises the amino acid sequence set forth in SEQ ID NO: 1 or 2.

5. The engineered microorganism of any one of claims 1-4, wherein the first gene is a CysE gene.

6. The engineered microorganism of claim 5, wherein the CysE gene comprises the nucleic acid sequence set forth in SEQ ID NO: 2 or 4.

7. The engineered microorganism of any one of claims 1-6, wherein the cysteine synthase A comprises the amino acid sequence set forth in SEQ ID NO:

5.

8. The engineered microorganism of any one of claims 1-7, wherein the second gene is a CysK gene.

9. The engineered microorganism of claim 8, wherein the CysK gene comprises the nucleic acid sequence set forth in SEQ ID NO:

6.

10. The engineered microorganism of any one of claims 1-9, wherein the engineered microorganism converts H2S to L-cysteine. 133 FH12512877.6Attorney Docket No.: NEX-16225 11. The engineered microorganism of any one of claims 1-10, further comprising a third gene encoding a glutathione biosynthesis bifunctional protein or encoding a glutamate- cysteine ligase (ghsA) and a glutathione synthase (gshB).

12. The engineered microorganism of claim 11, wherein the third gene encodes the glutathione biosynthesis bifunctional protein.

13. The engineered microorganism of claim 12, wherein the glutathione biosynthesis bifunctional protein comprises the amino acid sequence set forth in SEQ ID NO: 7 or 9.

14. The engineered microorganism of claim 12 or 13, wherein the third gene is a gshF (gshAB) gene.

15. The engineered microorganism of claim 14, wherein the gshF gene comprises the nucleic acid sequence set forth in SEQ ID NO: 8 or 10.

16. The engineered microorganism of claim 11, wherein the third gene encodes the glutamate-cysteine ligase and the glutathione synthase.

17. The engineered microorganism of claim 16, wherein the glutamate-cysteine ligase comprises the amino acid sequence set forth in SEQ ID NO:

11.

18. The engineered microorganism of claim 16 or 17, wherein the glutathione synthase comprises the amino acid sequence set forth in SEQ ID NO:

13.

19. The engineered microorganism of any one of claims 16-18, wherein the third gene comprises a gshA gene and a gshB gene.

20. The engineered microorganism of claim 19, wherein the gshA gene comprises the nucleic acid sequence set forth in SEQ ID NO:

12.

21. The engineered microorganism of claim 19, wherein the gshB gene comprises the nucleic acid sequence set forth in SEQ ID NO:

14. 134 FH12512877.6Attorney Docket No.: NEX-16225 22. The engineered microorganism of any one of claims 11-21, wherein the engineered microorganism converts H2S to L-cysteine, converts L-cysteine to gamma-L-glutamyl-L- cysteine, and converts gamma-L-glutamyl-L-cysteine to glutathione.

23. The engineered microorganism of any one of claims 1-22, wherein the engineered microorganism lacks native decR (DNA-binding transcriptional activator), iscS (cysteine desulfurase), yhaM (L-cysteine desulfidase) and / or yhaO (L-cysteine importer).

24. The engineered microorganism of claim 23, wherein the decR comprises the amino acid sequence set forth in SEQ ID NO: 37 or encoded by the nucleic acid set forth in SEQ ID NO:

38.

25. The engineered microorganism of claim 23, wherein the iscS comprises the amino acid sequence set forth in SEQ ID NO: 35 or encoded by the nucleic acid set forth in SEQ ID NO:

36.

26. The engineered microorganism of claim 23, wherein the yhaM comprises the amino acid sequence set forth in SEQ ID NO: 25 or encoded by the nucleic acid set forth in SEQ ID NO:

26.

27. The engineered microorganism of claim 23, wherein the yhaO comprises the amino acid sequence set forth in SEQ ID NO: 27 or encoded by the nucleic acid set forth in SEQ ID NO:

28.

28. The engineered microorganism of any one of claims 1-30, wherein the first gene, the second gene, the third gene, and / or the fourth gene is a heterologous or homologous gene.

29. The engineered microorganism of any one of claims 1-28, wherein the first gene, the second gene, and / or the third gene is operably linked to a promoter that is activated or repressed by an environmental cue. 135 FH12512877.6Attorney Docket No.: NEX-16225 30. The engineered microorganism of claim 29, wherein the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL).

31. The engineered microorganism of claim 29 or 30, wherein the promoter is a ROS- activated promoter.

32. The engineered microorganism of claim 31, wherein the ROS-activated promoter is a oxyS promoter is an ROS-activated promoter.

33. The engineered microorganism of claim 32, wherein the oxyS promoter is from E. coli.

34. The engineered microorganism of any one of claims 31-33, wherein the engineered microorganism expresses a transcription factor OyxR.

35. The engineered microorganism of claim 34, wherein ROS activates the OxyR, which activates the native OxyS promoter from E. coli.

36. The engineered microorganism of any one of claims 33-35, wherein the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO:

41.

37. The engineered microorganism of any one of claims 34-36, wherein the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO:

40.

38. The engineered microorganism of claim 29 or 30, wherein the promoter is a luminal H2S-activated promoter .

39. The engineered microorganism of claim 38, wherein the luminal H2S-activated promoter is an IR9 promoter.

40. The engineered microorganism of claim 39, wherein the IR9 promoter is from B. licheniformis. 136 FH12512877.6Attorney Docket No.: NEX-16225 41. The engineered microorganism of any one of claims 38-40, wherein the engineered microorganism expresses NreB and NreC.

42. The engineered microorganism of claim 41, wherein the NreB and NreC are from B. licheniformis.

43. The engineered microorganism of claim 41 or 42 , wherein the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter.

44. The engineered microorganism of any one of claims 39-43, wherein the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

46.

45. The engineered microorganism of any one of claims 41-44, wherein the NreB comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO:

43.

46. The engineered microorganism of any one of claims 41-45, wherein the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO:

45.

47. The engineered microorganism of claim 29 or 30, wherein the promoter is a thiosulfate-activated promoter.

48. The engineered microorganism of claim 47, wherein the thiosulfate-activated promoter is a phsA342 promoter.

49. The engineered microorganism of claim 48, wherein the phsA342 promoter is from S. halifaxensis.

50. The engineered microorganism of any one of claims 47-49, wherein the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor.

51. The engineered microorganism of claim 50, wherein the thiosulfate sensor is thsS. 137 FH12512877.6Attorney Docket No.: NEX-16225 52. The engineered microorganism of claim 50 or 51, wherein the transcription factor is thsR.

53. The engineered microorganism of claim 52, wherein the thsR from S. halifaxensis.

54. The engineered microorganism of any one of claims 50-53, wherein the activated transcription factor, thsR, activates the promoter phsA342.

55. The engineered microorganism of any one of claims 48-54, wherein the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

51.

56. The engineered microorganism of any one of claims 51-55, wherein the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO:

48.

57. The engineered microorganism of any one of claims 52-56, wherein the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or encoded by the nucleic acid set forth in SEQ ID NO:

50.

58. The engineered microorganism of claim 29 or 30, wherein the promoter is an interleukin- or pro-inflammatory protein-activated promoter.

59. The engineered microorganism of claim 58, wherein the Interleukin (IL) is IL-1, IL-4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL- 39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1.

60. The engineered microorganism of claim 58 or 59, wherein the engineered microorganism expresses a transcription factor which is activated by an Interleukin or a pro- inflammatory protein. 138 FH12512877.6Attorney Docket No.: NEX-16225 61. The engineered microorganism of claim 60, wherein the activated transcription factor activates the promoter.

62. The engineered microorganism of any one of claims 29-61, wherein the engineered microorganism expresses a sulfide quinone reductase (SQR) enzyme.

63. The engineered microorganism of claim 62, wherein sulfide quinone reductase (SQR) enzyme is from Rhodobacter Capsulatus or Wolinella succinogenes.

64. The engineered microorganism of claim 62 or 63, wherein the sulfide quinone reductase (SQR) enzyme comprises the amino acid sequence set forth in SEQ ID NO: 15 or 17 or encoded by the nucleic acid set forth in SEQ ID NO: 16 or 18.

65. The engineered microorganism of any one of claims 1-64, wherein the engineered microorganism is a bacterium.

66. The engineered microorganism of claim 65, wherein the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium.

67. The engineered microorganism of claim 65 or 66, wherein the bacterium is Escherichia coli strain Nissle, MG1655, or S1030.

68. The engineered microorganism of any one of claims 65-67, wherein the bacterium is an auxotroph in a gene that is important for cellular growth.

69. The engineered microorganism of claim 68, wherein the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof.

70. The engineered microorganism of any one of claims 65-69, wherein the bacterium comprises a kill switch. 139 FH12512877.6Attorney Docket No.: NEX-16225 71. A pharmaceutically acceptable composition comprising the microorganism of any one of claims 1-70; and a pharmaceutically acceptable carrier.

72. The pharmaceutically acceptable composition of claim 71, wherein the composition is formulated for oral or rectal administration.

73. An engineered microorganism, comprising: a first gene encoding a desulfidase.

74. The engineered microorganism of claim 73, wherein the desulfidase comprises the amino acid sequence set forth in SEQ ID NO:

25.

75. The engineered microorganism of claim 73 or 74, wherein the first gene is a yhaM gene.

76. The engineered microorganism of claim 75, wherein the yhaM gene comprises the nucleic acid sequence set forth in SEQ ID NO:

26.

77. The engineered microorganism of any one of claims 73-76 wherein the engineered microorganism converts L-cysteine to H2S.

78. The engineered microorganism of any one of claims 73-77, further comprising a second gene encoding a peptidase T, a third gene encoding a glutathione hydrolase, and a fourth gene encoding an aminopeptidase B.

79. The engineered microorganism of claim 78, wherein the peptidase T comprises the amino acid sequence set forth in SEQ ID NO:

19.

80. The engineered microorganism of claim 78 or 79, wherein the second gene is a pepT gene.

81. The engineered microorganism of claim 80, wherein the pepT gene comprises the nucleic acid sequence set forth in SEQ ID NO:

20. 140 FH12512877.6Attorney Docket No.: NEX-16225 82. The engineered microorganism of any one of claims 78-81, wherein the glutathione hydrolase comprises the amino acid sequence set forth in SEQ ID NO:

23.

83. The engineered microorganism of any one of claims 78-82, wherein the third gene is a ggt gene.

84. The engineered microorganism of claim 83, wherein the ggt gene comprises the nucleic acid sequence set forth in SEQ ID NO:

24.

85. The engineered microorganism of any one of the claims 78-84, wherein the aminopeptidase B comprises the amino acid sequence set forth in SEQ ID NO:

21.

86. The engineered microorganism of any one of claims 78-85, wherein the fourth gene is a pepB gene.

87. The engineered microorganism of claim 86, wherein the pepB gene comprises the nucleic acid sequence set forth in SEQ ID NO:

22.

88. The engineered microorganism of any one of claims 78-87, wherein the engineered microorganism converts glutathione to L-Cysteinylglycine, L-Cysteinylglycine to L-cysteine, and L-cysteine to H2S.

89. The engineered microorganism of any one of claims 73-88, further comprising a fifth gene encoding a L-cysteine importer.

90. The engineered microorganism of claim 89, wherein the L-cysteine importer comprises the amino acid sequence set forth in SEQ ID NO:

27.

91. The engineered microorganism of claim 89 or 90, wherein the fifth gene is a yhaO gene.

92. The engineered microorganism of claim 91, wherein the yhaO gene comprises the nucleic acid sequence set forth in SEQ ID NO:

28. 141 FH12512877.6Attorney Docket No.: NEX-16225 93. The engineered microorganism of any one of claims 73-92, wherein the first gene, the second gene, the third gene, the fourth gene, and / or the fifth gene is a heterologous or homologous gene.

94. The engineered microorganism of any one of claims 73-93, wherein the first gene, the second gene, the third gene, the fourth gene, and / or the fifth gene is operably linked to a promoter that is activated or repressed by an environmental cue.

95. The engineered microorganism of claim 94, wherein the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL).

96. The engineered microorganism of claim 94 or 95, wherein the promoter is a ROS- activated promoter.

97. The engineered microorganism of claim 96, wherein the ROS-activated promoter is a oxyS promoter is an ROS-activated promoter.

98. The engineered microorganism of claim 97, wherein the oxyS promoter is from E. coli.

99. The engineered microorganism of any one of claims 96-98, wherein the engineered microorganism expresses a transcription factor OyxR.

100. The engineered microorganism of claim 99, wherein ROS activates the OxyR, which activates the native OxyS promoter from E. coli.

101. The engineered microorganism of any one of claims 98-100, wherein the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO:

41.

102. The engineered microorganism of any one of claims 99-101, wherein the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO:

40. 142 FH12512877.6Attorney Docket No.: NEX-16225 103. The engineered microorganism of claim 94 or 95, wherein the promoter is a luminal H2S-activated promoter .

104. The engineered microorganism of claim 103, wherein the luminal H2S-activated promoter is an IR9 promoter.

105. The engineered microorganism of claim 104, wherein the IR9 promoter is from B. licheniformis.

106. The engineered microorganism of any one of claims 103-105, wherein the engineered microorganism expresses NreB and NreC.

107. The engineered microorganism of claim 106, wherein the NreB and NreC are from B. licheniformis.

108. The engineered microorganism of claim 106 or 107 , wherein the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter.

109. The engineered microorganism of any one of claims 104-108, wherein the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

46.

110. The engineered microorganism of any one of claims 106-109, wherein the NreB comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO:

43.

111. The engineered microorganism of any one of claims 106-110, wherein the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO:

45.

112. The engineered microorganism of claim 94 or 95, wherein the promoter is a thiosulfate-activated promoter. 143 FH12512877.6Attorney Docket No.: NEX-16225 113. The engineered microorganism of claim 112, wherein the thiosulfate-activated promoter is a phsA342 promoter.

114. The engineered microorganism of claim 113, wherein the phsA342 promoter is from S. halifaxensis.

115. The engineered microorganism of any one of claims 112-114, wherein the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor.

116. The engineered microorganism of claim 115, wherein the thiosulfate sensor is thsS.

117. The engineered microorganism of claim 115 or 116, wherein the transcription factor is thsR.

118. The engineered microorganism of claim 117, wherein the thsR from S. halifaxensis.

119. The engineered microorganism of any one of claims 115-118, wherein the activated transcription factor, thsR, activates the promoter phsA342.

120. The engineered microorganism of any one of claims 113-119, wherein the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

51.

121. The engineered microorganism of any one of claims 116-120, wherein the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO:

48.

122. The engineered microorganism of any one of claims 117-121, wherein the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or encoded by the nucleic acid set forth in SEQ ID NO:

50.

123. The engineered microorganism of claim 94 or 95, wherein the promoter is an interleukin- or a pro-inflammatory protein-activated promoter. 144 FH12512877.6Attorney Docket No.: NEX-16225 124. The engineered microorganism of claim 123, wherein the Interleukin (IL) is IL-1, IL- 4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1.

125. The engineered microorganism of claim 123 or 124, wherein the engineered microorganism expresses a transcription factor which is activated by an interleukin or a pro- inflammatory protein.

126. The engineered microorganism of claim 125, wherein the activated transcription factor activates the promoter.

127. The engineered microorganism of any one of claims 73-126, wherein the engineered microorganism is a bacterium 128. The engineered microorganism of claim 127, wherein the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium.

129. The engineered microorganism of claim 127, wherein the bacterium is Escherichia coli strain Nissle, MG1655, or S1030.

130. The engineered microorganism of any one of claims 127-129, wherein the bacterium is an auxotroph in a gene that is important for cellular growth.

131. The engineered microorganism of claim 130, wherein the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof.  145 FH12512877.6Attorney Docket No.: NEX-16225 132. The engineered microorganism of any one of claims 127-131, wherein the bacterium comprises a kill switch.

133. A pharmaceutically acceptable composition comprising the microorganism of any one of claims 73-132; and a pharmaceutically acceptable carrier.

134. The composition of claim 133, wherein the pharmaceutically acceptable composition is formulated for oral or rectal administration.

135. An engineered microorganism comprising a first gene and a second gene encoding two subunits of a sulfite reductase.

136. The engineered microorganism of claim 135, wherein the sulfite reductase comprises the amino acid sequence set forth in SEQ ID NO: 29 or 31.

137. The engineered microorganism of claim 135 or 136, wherein the first gene is a CysI gene and the second gene is a CysJ gene.

138. The engineered microorganism of claim 137, wherein the CysI gene comprises the nucleic acid sequence set forth in SEQ ID NO:

30.

139. The engineered microorganism of claim 137, wherein the CysJ gene comprises the nucleic acid sequence set forth in SEQ ID NO:

32.

140. The engineered microorganism of any one of claims 135-139, further comprising a third gene encoding a siroheme synthetase.

141. The engineered microorganism of claim 140, wherein the siroheme synthetase comprises the amino acid sequence set forth in SEQ ID NO:

33.

142. The engineered microorganism of claim 140 or 141, wherein the third gene is a CysG gene. 146 FH12512877.6Attorney Docket No.: NEX-16225 143. The engineered microorganism of claim 142, wherein the CysG gene comprises the nucleic acid sequence set forth in SEQ ID NO:

34.

144. The engineered microorganism of any one of claims 135-143, wherein the engineered microorganism converts sulfite to H2S.

145. The engineered microorganism of any one of claims 135-144, wherein the first gene, the second gene, and / or the third gene is a heterologous or homologous gene.

146. The engineered microorganism of any one of claims 135-145, wherein the first gene, the second gene, and / or the third gene is operably linked to a promoter that is activated or repressed by an environmental cue.

147. The engineered microorganism of claim 146, wherein the environmental cue is luminal H2S, reactive oxygen species (ROS), thiosulfate, a disease-relevant biomarker, or Interleukin (IL).

148. The engineered microorganism of claim 146 or 147, wherein the promoter is a ROS- activated promoter.

149. The engineered microorganism of claim 148, wherein the ROS-activated promoter is a oxyS promoter is an ROS-activated promoter.

150. The engineered microorganism of claim 149, wherein the oxyS promoter is from E. coli.

151. The engineered microorganism of any one of claims 148-150, wherein the engineered microorganism expresses a transcription factor OyxR.

152. The engineered microorganism of claim 151, wherein ROS activates the OxyR, which activates the native OxyS promoter from E. coli.

153. The engineered microorganism of any one of claims 149-152, wherein the OxyS comprises the nucleic acid sequence set forth in SEQ ID NO:

41. 147 FH12512877.6Attorney Docket No.: NEX-16225 154. The engineered microorganism of any one of claims 151-153, wherein the OxyR comprises the amino acid sequence set forth in SEQ ID NO: 39 or encoded by the nucleic acid set forth in SEQ ID NO:

40.

155. The engineered microorganism of claim 146 or 147, wherein the promoter is a luminal H2S-activated promoter.

156. The engineered microorganism of claim 155, wherein the luminal H2S-activated promoter is an IR9 promoter.

157. The engineered microorganism of claim 156, wherein the IR9 promoter is from B. licheniformis.

158. The engineered microorganism of any one of claims 155-157, wherein the engineered microorganism expresses NreB and NreC.

159. The engineered microorganism of claim 158, wherein the NreB and NreC are from B. licheniformis.

160. The engineered microorganism of claim 158 or 159, wherein the NreB senses H2S and phosphorylates the NreC, which activates the IR9 promoter.

161. The engineered microorganism of any one of claims 156-160, wherein the IR9 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

46.

162. The engineered microorganism of any one of claims 158-161, wherein the NreB comprises the amino acid sequence set forth in SEQ ID NO: 42 or encoded by the nucleic acid set forth in SEQ ID NO:

43.

163. The engineered microorganism of any one of claims 158-162, wherein the NreC comprises the amino acid sequence set forth in SEQ ID NO: 44 or encoded by the nucleic acid set forth in SEQ ID NO:

45. 148 FH12512877.6Attorney Docket No.: NEX-16225 164. The engineered microorganism of claim 146 or 147, wherein the promoter is a thiosulfate-activated promoter.

165. The engineered microorganism of claim 164, wherein the thiosulfate-activated promoter is a phsA342 promoter.

166. The engineered microorganism of claim 165, wherein the phsA342 promoter is from S. halifaxensis.

167. The engineered microorganism of any one of claims 164-166, wherein the engineered microorganism expresses a thiosulfate sensor, which activates a transcription factor.

168. The engineered microorganism of claim 167, wherein the thiosulfate sensor is thsS.

169. The engineered microorganism of claim 167 or 168, wherein the transcription factor is thsR.

170. The engineered microorganism of claim 169, wherein the thsR from S. halifaxensis.

171. The engineered microorganism of any one of claims 167-170, wherein the activated transcription factor, thsR, activates the promoter phsA342.

172. The engineered microorganism of any one of claims 165-171, wherein the phsA342 promoter comprises the nucleic acid sequence set forth in SEQ ID NO:

51.

173. The engineered microorganism of any one of claims 168-172, wherein the thsS comprises the amino acid sequence set forth in SEQ ID NO: 47 or encoded by the nucleic acid set forth in SEQ ID NO:

48.

174. The engineered microorganism of any one of claims 169-173, wherein the thsR comprises the amino acid sequence set forth in SEQ ID NO: 49 or encoded by the nucleic acid set forth in SEQ ID NO:

50. 149 FH12512877.6Attorney Docket No.: NEX-16225 175. The engineered microorganism of claim 145 or 146, wherein the promoter is an interleukin- or a pro-inflammatory protein-activated promoter.

176. The engineered microorganism of claim 175, wherein the Interleukin (IL) is IL-1, IL- 4, IL-5 IL-6, IL-8, IL-10, IL-11, IL-13, IL-17A, IL-17F, IL-27, IL-28, IL-29, IL-36, IL-38, IL-39, or IL-40 or the pro-inflammatory protein is tumor necrosis factor (TNF), TNF-alpha, TNF-beta, C-reactive protein (CRP), chemokine ligands (CCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, C-X-C motif chemokine ligand (CXCL) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, XCL1, XCL2, or CX3CL1.

177. The engineered microorganism of claim 175 or 176, wherein the engineered microorganism expresses a transcription factor which is activated by an interleukin or a pro- inflammatory protein.

178. The engineered microorganism of claim 177, wherein the activated transcription factor activates the promoter.

179. The engineered microorganism of any one of claims 135-178, wherein the engineered microorganism is a bacterium.

180. The engineered microorganism of claim 179, wherein the bacterium is selected from the group consisting of Bacillus, Bacteroides, Bifidobacterium, Clostridium, Corynebacterium, Escherichia, Lactobacillus, Lactococcus, Pseudomonas, Streptomyces, or Mycobacterium.

181. The engineered microorganism of claim 179, wherein the bacterium is Escherichia coli strain Nissle, MG1655, or S1030.

182. The engineered microorganism of any one of claims 179-181, wherein the bacterium is an auxotroph in a gene that is important for cellular growth. 150 FH12512877.6Attorney Docket No.: NEX-16225 183. The engineered microorganism of claim 182, wherein the gene that is important for cellular growth is dapA, xylA, thyA, tyrA, glnA, cysE, metA, thrC, aspC, hisG, tyrB, proC, lysA, asnA, asnB, or any combination thereof.

184. The engineered microorganism of any one of claims 179-183, wherein the bacterium comprises a kill switch.

185. A pharmaceutically acceptable composition comprising the microorganism of any one of claims 135-184; and a pharmaceutically acceptable carrier.

186. The composition of claim 185, wherein the pharmaceutically acceptable composition is formulated for oral or rectal administration.

187. A method of treating a disease associated with increased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism of any one of claims 1-70 or the pharmaceutically acceptable composition of claim 71 or 72.

188. The method of claim 187, wherein the disease associated with increased H2S levels is a neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), an ulcer, colorectal cancer, mental retardation, Down Syndrome, intestinal pain, H2S poisoning, an inflammatory disease, a cardiometabolic disease, Ethylmalonic encephalopathy, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus.

189. A method of treating a disease associated with decreased H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism of any one of claims 73-132 and 135-184 or the pharmaceutically acceptable composition of claim 133, 134, 185, or 186. 151 FH12512877.6Attorney Docket No.: NEX-16225 190. The method of claim 189, wherein the disease associated with decreased H2S levels neurodegenerative disease, a myocardial injury, an ophthalmic disease, a gastrointestinal disorder, an ulcer, colorectal cancer, intestinal pain, an inflammatory disease, a cardiometabolic disease, liver fibrosis, liver ischemia‒reperfusion injury, hepatocellular carcinoma, hepatotoxicity, acute liver failure, osteoporosis, central nervous diseases like Alzheimer's disease, Parkinson’s disease, Huntington’s disease, and ischemic stroke, skin diseases such as burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, pruritus.

191. A method of reducing H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism of any one of claims 1-70 or the pharmaceutically acceptable composition of claim 71 or 72.

192. A method of increasing H2S levels, comprising administering to a subject in need thereof an effective amount of the engineered microorganism of any one of claims 73-132 and 135-184 or the pharmaceutically acceptable composition of claim 133, 134, 185, or 186.

193. A method of modulating H2S levels based on an environmental cue comprising administering to a subject in need thereof an effective amount of the engineered microorganism of any one of claims 29-70, 94-132 and 146-184.

194. A method of reducing H2S levels in environmental water or wastewater, comprising administering thereof an effective amount of the engineered microorganism of any one of claims 1-70. 152 FH12512877.6

Images