Methods and materials for treating disorders related to bacterial infections

Abstract

Described herein are chimeric bacteriophage particles including recombinant phagemids and methods of treating a bacterial infection (e.g., a Shigella infection) using the same. Recombinant phagemids can include CRISPR-Cas systems that target virulence factors.

Description

[0001]Attorney Docket No.29539-0809WO1 METHODS AND MATERIALS FOR TREATING DISORDERS RELATED TO BACTERIAL INFECTIONS CLAIM OF PRIORITY This application claims the benefit of U.S. Provisional Application Serial No. 63 / 571,957, filed on March 29, 2024. The entire contents of the foregoing are incorporated herein by reference. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “29539-0809WO1_SL_ST26.XML.” The XML file, created on March 28, 2025, is 525,037 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with Government support under Grant No. AI146405 awarded by the National Institutes of Health. The Government has certain rights in the invention. TECHNICAL FIELD Provided herein are compositions including bacteriophage. For example, described are bacteriophage compositions containing at least one strain of genetically engineered bacteriophage containing an effector molecule that targets bacteria, such as Shigella spp., and methods for using bacteriophage compositions to treat symptoms or diseases caused by Shigella, such as shigellosis.   BACKGROUND Shigella bacteria can cause an infection called shigellosis (also called dysentery). Shigella was the second-leading cause of diarrheal mortality in 2016 among all ages, and the leading bacterial cause of diarrhea, accounting for approximately 212000 deaths and about 13% of all diarrhea- associated deaths. See, for example, who.int / teams / immunization- vaccines-and-biologicals / diseases / shigella. Symptoms associated with shigellosis include diarrhea, fever, and stomach pain. Disease results from bacterial adherence to, or invasion of, the epithelial cells lining the gastrointestinal tract, inducing watery or bloody diarrhea. See, Attorney Docket No.29539-0809WO1 for example, Schroeder & Hilbi Clin. Microbiol. Rev.21, pp.134–156 (2008). Infections in low- and middle-income countries are predominant in children and frequent in adults, while infections in high-income nations are linked to travel, pediatric and adult care centers, and foodborne, waterborne, or urban-centric outbreaks. See, for example, Kotloff et al., Lancet 382, pp.209–222 (2013); Arvelo et al., Pediatr. Infect. Dis. J.28, pp.976–980 (2009); and Tansarli et ai., Lancet Infect Dis.2023 Jun;23(6):740-750. While treatment with some antibiotics may shorten the amount of time that symptoms are experienced, resistance to antibiotics commonly used to treat Shigella have been increasing at least since 2016. For example, about 242,000 antimicrobial-resistant Shigella infections, over 50% of Shigella infections, occur in the United States each year. See, for example, cdc.gov / shigella / index.html. Therefore, there is a need for alternative methods to treat shigellosis and Shigella infections that do not rely on antibiotic administration. SUMMARY Described herein are methods of making and using a chimeric bacteriophage particle comprising: a) a recombinant phagemid comprising, in any order: i) a nucleotide sequence encoding a CRISPR RNA (crRNA) comprising i) one or more spacer sequence(s) that is complementary to one or more target nucleotide sequence(s) encoding one or more virulence factor(s) in a bacterial species, and wherein the one or more spacer sequences(s) are located between a first inverted repeat sequence and a second inverted repeat sequence; ii) a nucleotide sequence encoding a tracrRNA; iii) a nucleotide sequence encoding a CRISPR-associated (cas) nuclease; iv) a nucleotide sequence comprising a bacteriophage packaging (pac) site; v) a nucleotide sequence comprising a bacteriophage origin of replication; and vi) optionally, a nucleotide sequence encoding a non-native tail fiber or variant thereof, wherein the non-native tail fiber or variant thereof is from a bacteriophage that can infect a bacterial strain and b) one or more tail fibers, wherein the one or more tail fibers is a non-native tail fiber or variant thereof. Attorney Docket No.29539-0809WO1 In some embodiments, the bacterial stain is a strain of Shigella or Escherichia. In some embodiments, the virulence factor is selected from ipaH4, mxiH, mxiD, virB, iutA, and sitA. In some embodiments, the spacer sequence has at least 80-100% (e.g., 90%, 95%, or 100%) sequence identity to SEQ ID NOs.14-31. In some embodiments, the cas nuclease is a Cas9 nuclease. In some embodiments, the cas nuclease is a Streptococcus pyogenes Cas9 nuclease, a Staphylococcus aureus Cas9 nuclease, a homolog thereof, or a variant thereof. In some embodiments, the nucleotide sequence encoding the cas nuclease has at least 90%, 95%, or 100% sequence identity to SEQ ID NO: 32. In some embodiments, the nucleotide sequence comprising the pac site has at least 90%, 95%, or 100% sequence identity to SEQ ID NO: 34. In some embodiments, the nucleotide sequence comprising the bacteriophage origin of replication has at least 90%, 95%, or 100% sequence identity to SEQ ID NO: 35. In some embodiments, the nucleotide sequence encoding the non-native tail fiber or variant thereof has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO: 33. Preferably, the nucleotide sequence encoding the non-native tail fiber or variant thereof has at least 90%, 95%, or 100% sequence identity to SEQ ID NO: 33. In some embodiments, the nucleotide sequence encoding the non-native tail fiber or variant thereof has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to SEQ ID NO: 38. Preferably, the nucleotide sequence encoding the non-native tail fiber or variant thereof has at least 90%, 95%, or 99% sequence identity to SEQ ID NO: 38. In some embodiments, the nucleotide sequence encoding the non- native tail fiber or variant thereof has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to SEQ ID NO: 39. Preferably, the nucleotide sequence encoding the non-native tail fiber or variant thereof has at least 90%, 95%, or 99% sequence identity to SEQ ID NO: 39. In some embodiments, the plurality of the chimeric bacteriophage particles, as described in any of the embodiments above, has a transducing particle titer from about 103to about 1014(preferably, about 107to about 1014) in a broth infection assay, wherein the broth infection assay comprises a recipient cell selected from S. dysenteriae, S. flexneri, S. boydii, S. sonnei, and Escherichia coli (E. coli). Also provided herein are chimeric bacteriophage particle libraries comprising a plurality of unique chimeric bacteriophage particles, wherein each of the unique chimeric Attorney Docket No.29539-0809WO1 bacteriophage particles comprises the chimeric bacteriophage particle of any of the above- described embodiments, wherein the nucleotide sequence is a unique nucleotide sequence encoding a unique non-native tail fiber or variant thereof. Also provided herein are genetically modified lytic bacteriophages comprising: one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis; and, optionally, a non-native tail fiber or variant thereof from a bacteriophage. In some embodiments, the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis comprises one or more of the following genes from Φ2457T: ORF53, ORF54, ORF55, ORF56, ORF57, ORF64, ORF65, and / or ORF66. In some embodiments, the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis comprises: a mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof; a mutated nucleotide sequence encoding a non-functional DNA helicase or homolog thereof; or a mutated nucleotide sequence encoding a non-functional lysin or homolog thereof. In some embodiments, the mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof is a mutated ORF54 gene encoding a non-functional ORF54 gene product. In some embodiments, the non-functional DnaA protein or homolog thereof is a truncated DnaA protein or homolog thereof. In some embodiments, the mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof comprises an amber mutation. In some embodiments, the mutated nucleotide sequence encoding a non- functional DNA helicase or homolog thereof is a mutated ORF55 gene encoding a non- functional ORF55 gene product. In some embodiments, the non-functional DNA helicase or homolog thereof is a truncated DNA helicase or homolog thereof. In some embodiments, the mutated nucleotide sequence encoding a non-functional DNA helicase or homolog thereof comprises an amber mutation. In some embodiments, the mutated nucleotide sequence encoding a non-functional lysin or homolog thereof is a mutated ORF65 gene encoding a non-functional ORF65 gene product. In some embodiments, the non-functional lysin or homolog thereof is a truncated lysin or homolog thereof. In some embodiments, the mutated nucleotide sequence encoding a non-functional lysin or homolog thereof comprises an amber mutation. In some embodiments, the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis Attorney Docket No.29539-0809WO1 comprises deletion or truncation of a nucleotide sequence encoding a tail fiber protein or variant thereof. In some embodiments, the tail fiber or variant thereof is from a bacteriophage that can infect Shigella. In some embodiments, the genetically modified bacteriophage cannot replicate in bacterial cells lacking amber suppressor transfer RNAs. In some embodiments, the genetically modified bacteriophage only replicates in bacterial cells comprising amber suppressor transfer RNAs. In some embodiments, the bacterial cells are Shigella cells. Also included herein are genetically modified bacteria cells comprising a vector, wherein the vector comprises one or more nucleotide sequences encoding one or more amber suppressor transfer RNA (tRNA). In some embodiments, the vector is an exogenously added vector. In some embodiments, the one or more nucleotide sequences encoding one or more amber suppressor tRNA encodes a supF amber suppressor tRNA. In some embodiments, the one or more nucleotide sequences encoding one or more amber supper tRNAs is operably linked to a constitutive promoter. In some embodiments, the genetically modified bacteria cell is a genetically modified Shigella cell (e.g., a Shigella flexneri cell). In some embodiments, the genetically modified bacteria cells further comprise a nucleotide sequence encoding a modified tail fiber or variant thereof of a bacteriophage that can infect a strain of Shigella that is not a Φ2457T bacteriophage. In some embodiments, the modified tail fiber or variant thereof is encoded by ORF14 of the Shigella bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33), or a nucleotide sequence having at least 90%, 95%, or 99% sequence identity thereto. In some embodiments, the modified tail fiber or variant thereof is encoded by a nucleotide sequence having at least 90%, 95%, or 99% sequence identity to phi2457T ORF52 (SEQ ID NO: 38) or phi2457T ORF46 (SEQ ID NO: 39). In some embodiments, the nucleic acid encoding a tail fiber or variant thereof is operably linked to a promoter. In some embodiments, the promoter is a Φ2457T ORF52 promoter or a Φ2457T ORF46 promoter. Also described herein are systems for producing the chimeric bacteriophage of any of the embodiments described herein, wherein the system comprises, the genetically modified bacteriophage, as described herein, and the genetically modified bacteria cells, as described herein. Also provided herein are pharmaceutical compositions comprising the chimeric bacteriophage particle of any of the embodiments described herein. Included also are methods of treating a subject previously identified as having a bacterial infection, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising the chimeric bacteriophage particle of any of the above-described embodiments. In some embodiments, the bacterial infection is a Shigella Attorney Docket No.29539-0809WO1 infection. In some embodiments, the subject is a mammal (e.g., human or a non-human primate). In some embodiments, the subject is a human or a non-human primate. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier is a pharmaceutically acceptable excipient. In some embodiments, the method further comprises administering to the subject an effective amount of a second therapeutic agent comprising an anti-diarrheal and / or a rehydration solution. In some embodiments, the second therapeutic agent is an anti-diarrheal comprising bismuth subsalicylate (e.g., PEPTO-BISMOL® or KAOPECTATE®). In some embodiments, the rehydration solution is selected from an oral rehydration solution (e.g., PEDIALYTE® or LIQUID I.V. ®) and an intravenous rehydration solution. As used herein, the term “about” is used synonymously with the term “approximately.” Unless otherwise indicated, the use of the term “about” with regard to an amount includes values plus or minus 10% of the stated value. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the subject matter herein, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. DESCRIPTION OF DRAWINGS FIG.1. ΦRGN phagemid construction for virulence factor (VF) targeting in Shigella. Bacterial donor cells harboring RGN phagemids encoding Cas9 (white) and spacers specific for virulence genes (black) are infected with genetically-engineered Φ2457T helper phages. Phagemids are packaged via recognition of the pac site (dark grey) to create ΦRGN Attorney Docket No.29539-0809WO1 transducing particles. Upon recipient bacterial cell infection, RGNs cleave pathogen-specific VF sequences (e.g., in Shigella flexneri) to induce cell death or virulence plasmid loss but have no effect on commensal bacteria lacking VF sequences. FIGs.2A-2D. Engineering the Φ2457T phagemid packaging system. FIG.2A) Phagemid packaging into Φ2457T. S. flexneri donor cells with plasmids containing putative Φ2457T pac site and flanking DNA of increasing length (vector::pac1 and vector::pac2) or vector-only negative controls were infected by Φ2457T. Free nucleic acids in lysates were digested and encapsidated DNA was isolated. PCR identified Φ2457T genomic and phagemid DNA packaged into phages. FIG.2B) Creation of Φ2457Tam3 helper phages. Amber knockout mutations targeted ORFs 54, 55, and 65. Resulting Φ2457Tam3 phages were plated onto lawns of wild-type (right) and amber suppressor (left) S. flexneri strains. Clearings (plaques) represent phage infection. FIG.2C) Φ2457Tam3 helper phages efficiently transduce phagemids with the Φ2457T pac site. S. flexneri donor cells containing phagemids with the indicated Φ2457T sequence were infected with Φ2457Tam3 helper phages and resulting phage lysates were used to infect S. flexneri 2457T recipient cells. Bacteria transduced with each phagemid were obtained by antibiotic selection and transducing phage concentrations were enumerated. The logarithmic-scale TFU / mL for each phagemid donor lysate plotted (n=3, ±SD). FIG.2D) Φ2457T helper phage one-step growth curves. Wild-type and amber suppressor strains of S. flexneri were infected with Φ2457Tam3.1 helper phages at a multiplicity of infection (MOI) of 0.01. After five minutes of incubation at 37℃ to allow for phage adsorption, cultures were diluted, and the phage titer was determined at each indicated time point. The logarithmic-scale plaque-forming units (PFU) / mL are plotted at each time point (n=3, +SD). FIGs.3A-3B. ΦRGNs target conserved virulence genes to kill S. flexneri in vitro. FIG.3A) The efficacy of ΦRGNs targeting various Shigella virulence factors was analyzed in broth infections assays. S. flexneri donor cells with RGN phagemids harboring the indicated virulence gene spacer targets were infected with Φ2457T am3 helper phages and ΦRGNs in donor cell lysates were collected. WT S. flexneri 2457T recipient cells were infected with each ΦRGN at MOIs of 10 (black bars) and 50 (white bars) for 3 hrs, and surviving virulent cells were enumerated by plating onto TSB + Congo red indicator plates, where virulent cells form red colonies and avirulent cells form white colonies. The logarithmic-scale virulent colony-forming units (CFUs) / mL normalized to untreated controls are plotted for each ΦRGN (n=2, ±SD). FIG.3B) S. flexneri donor cells containing RGN phagemids with either a random spacer sequence or the virB-5 spacer sequence that targets Attorney Docket No.29539-0809WO1 the Shigella virB virulence gene were infected with Φ2457Tam3 helper phages at a multiplicity of infection (MOI; ratio of phages to bacteria) of one for 2 hrs. Subsequently, each ΦRGN was collected from donor cell lysates and used to infect WT S. flexneri 2457T recipient cells at a MOI of 50 for 3 hrs. Transduced recipient cells were selected by plating onto TSB + Congo red indicator plates supplemented with antibiotics, and eight representative transduced Shigella cells were further re-streaked onto fresh indicator plates. These indicator plates enable differentiation of virulent Shigella cells (red colonies) and avirulent Shigella cells (white colonies). Representative results of the indicator plate phenotypes for each isolate are shown, in which scanned images of the plates are provided and colony color are designated below the images. Grey circles represent red, virulent colonies; white circles represent white, avirulent colonies; and mixed circles represent a mixture of virulent and avirulent colonies. FIGs.4A-4B. Φ2457Tam3 helper phages deliver DNA payloads to several E. coli and Shigella strains. FIG.4A) Serial dilutions of wild-type (WT) Φ2457T phages were plated onto lawns of various WT Shigella and Escherichia coli strains. Clearings (plaques) represent phage infection. FIG.4B) S. flexneri donor cells harboring pac3mut-ORF55 phagemids were infected with Φ2457Tam3 helper phages and the resulting phage lysates were used to infect the various WT Shigella and E. coli recipient cells. Transduced bacteria containing each putative phagemid were obtained by antibiotic selection and the concentration of transducing phages was enumerated. The logarithmic-scale TFU / mL for each recipient strain was normalized to the transducing titer on S. flexneri 2457T and plotted (n=2 or n=3, ±SD). NT; no transductants. FIGs.5A-C. Methods to generate chimeric ΦRGN bacteriophage particles. FIG. 5A) Bacteriophage transducing particle tail fiber allele replacement. Bacterial donor cells are transformed with RGN phagemids encoding Cas9 (white), spacers specific for virulence genes (black), and various tail fiber alleles (shades of grey). Upon genetically-engineered Φ2457T helper phage infection, phagemids are packaged into phage capsids via recognition of the pac site (black dashed line) to create RGN transducing particles (ΦRGNs) assembled with the non-native tail fibers expressed from the phagemid (chimeric ΦRGNs). Upon recipient cell infection, non-native tail fibers (shades of grey) redirect chimeric ΦRGN bacteriophage particles to novel hosts (e.g., across the Shigella species) for RGN phagemid delivery and target sequence destruction. FIG.5B) Directed evolution of tail fiber variants. Phagemid-encoded tail fiber gene variants (shades of grey) are generated through random mutagenesis. Phagemid packaging generates chimeric bacteriophage transducing particles Attorney Docket No.29539-0809WO1 assembled with each tail fiber variant (shades of grey). Expanded host range tail fibers are selected following novel recipient strain infection. Multiples cycles of mutagenesis, transduction, and enrichment selects for tail fiber variants optimized for each host. FIG.5C) Enhancing transduction efficiency with chimeric bacteriophage transducing particle libraries. Wild-type and tail fiber variant library phagemids were transformed into S. flexneri amber suppressor strains. The resulting donor strains were infected with Φ2457Tam3ΔORF52::lacZ helper phages at a multiplicity of infection (MOI; ratio of phages to bacteria) of two for two hours. The resulting phage lysates were used to infect S. flexneri strain 2457T, S. sonnei strain 53G, S. dysenteriae strain 1617, and E. coli K12 strain MG1655 recipient cells. Transduced bacteria containing each putative phagemid were selected by plating the bacterial cells on media supplemented with antibiotics, and the concentration of transducing phages was enumerated. The logarithmic-scale transductant forming units (TFU) / mL of WT tail fiber transducing particles and tail fiber variant libraries on each recipient strain were normalized to the transduction efficiency on S. flexneri 2457T and plotted (n=3, ±SD). DETAILED DESCRIPTION One alternative to using antibiotics to treat Shigella infections is bacteriophage therapy, or treatment with lytic Shigella-specific bacteriophage, or viruses that specifically infect and kill Shigella bacteria. However, the use of lytic bacteriophages isolated from the environment can result in the evolution of bacteriophage resistance through a variety of bacteriophage resistance mechanisms, including receptor adaptations and host defense systems. See, for example, Egido et al, FEMS Microbiology Reviews, Volume 46, Issue 1, January 2022, fuab048, doi.org / 10.1093 / femsre / fuab048. However, many bacteriophage resistance mechanisms require the repeated exposure of a bacterial population to the bacteriophage to be activated or evolve. Genetically modifying bacteriophage to infect and kill a single host cell without producing bacteriophage progeny, and therefore without producing an active lytic bacteriophage infection is one way to avoid activating bacteriophage resistance mechanisms in a bacterial population and to maintain containment of the genetically modified bacteriophage. In addition, bacteriophages can be specific to a strain of bacteria, and only infect that single bacterial strain, or a small subset of bacterial strains. As such, choosing which Shigella strains that a specific genetically modified bacteriophage can infect (referred to as tuning the bacteriophage host range) would be beneficial. Therefore, provided herein are chimeric bacteriophage particles, genetically Attorney Docket No.29539-0809WO1 modified bacteriophages or systems comprising genetically modified bacteriophages and genetically modified host cells that include i) targeted CRISPR-Cas system based bacteria- killing mechanisms (for example, for killing Shigella), ii) that contain disrupted bacteriophage replication and / or host cell lysis systems such that bacteriophage cannot produce a lytic infection, and / or iii) that have tunable bacteriophage host ranges. Provided herein are chimeric bacteriophage particles including a recombinant phagemid and one or more tail fiber(s) of a non-native tail fiber or variant thereof. Recombinant Phagemids (RGN phagemid) Provided herein are recombinant phagemids that facilitate targeted CRISPR-based bacteria-killing mechanisms (e.g., killing of Shigella). A phagemid (also called a phasmid) is a DNA-based cloning vector that contains bacteriophage and plasmid properties. The DNA- based cloning vector can be a high-copy vector or a low-copy vector. Recombinant phagemids contain nucleic acids encoding one or more Cas nuclease(s), one or more crRNA(s), one or more tracrRNA(s), a packaging (pac) site, optionally, one or more tail fiber(s) or variants thereof (e.g., a non-native tail fiber or variant thereof), and, optionally, a plasmid and / or bacteriophage origin of replication. CRISPR-associated (Cas) nucleases Disclosed herein are recombinant phagemids that include one or more nucleotide sequence(s) encoding one or more CRISPR-associated (Cas) nuclease(s). Exemplary types of Cas nucleases that can be included on any of the recombinant phagemids disclosed herein include, but are not limited to, Cas9, Cas12a, and Cpf1 nucleases. “Cas9 nuclease” refers to a large group of endonucleases that catalyze the double stranded DNA cleavage in the CRISPR-Cas system. These polypeptides are well known in the art and many of their structures (sequences) are characterized (See, e.g., WO2013 / 176772; WO2013 / 188638). The domains for catalyzing the cleavage of the double stranded DNA are the RuvC domain and the HNH domain. The RuvC domain is responsible for nicking the negative (−) strand and the HNH domain is responsible for nicking the positive (+) strand (See, e.g., Gasiunas et al. PNAS 109(36):E2579-E2586 (Sep.4, 2012)). Exemplary Cas9 nucleases and orthologs thereof are shown in Table 1, and engineered protospacer-adjacent motif (PAM) or high- fidelity variants are shown in Table 2. Any of the one or more nucleotide sequence(s) encoding one or more Cas nuclease(s) can be operably linked to any appropriate promoter. Attorney Docket No.29539-0809WO1 Table 1. List of Exemplary Cas9 or Cas12a Orthologs Ortholog UniProt or GenBank Accession Number Streptococcus pyogenes Cas9 Q99ZW2.1 a e . s o e pay g e y a o -eae oogs Published HF / PAM-RGN PMID / US Mutations* Attorney Docket No.29539-0809WO1 Published HF / PAM-RGN PMID / US PGPUB Mutations* v ri nt A or A, Attorney Docket No.29539-0809WO1 Published HF / PAM-RGN PMID / US i nt P Mutations* v r GPUB A, CRISPR RNA (crRNA) Disclosed herein are recombinant phagemids that include one or more nucleotide sequence(s) encoding one or more CRISPR RNA(s) (crRNA(s)). A crRNA is used to identify a target DNA to cut with the Cas nuclease. A crRNA as used herein refers to a nucleotide sequence that includes one or more spacer sequence(s) and one or more inverted repeat sequence(s), or a portion thereof, linked to the 5′ end of each spacer sequence. The specific design of a crRNA will vary based on the CRISPR-Cas system in which the crRNA is to be used. The crRNAs of this invention are synthetic, made by man and not found in nature. In some embodiments, a crRNA may comprise, from 5′ to 3′, an inverted repeat sequence (full length or portion thereof (“handle”)), a spacer sequence, and a second inverted repeat sequence (full length or portion thereof). In some cases, a crRNA complexes with a tracrRNA, thereby forming a guide RNA (gRNA) for a Type II CRISPR-Cas system. In some embodiments, crRNA comprises at least one spacer sequence (having a 5′ end and a 3′ end) linked at its 3′ end to the 5′ end of at least one inverted repeat sequence or a portion of the least one inverted repeat sequence to form a “spacer-repeat sequence” having a 5′ end and a 3′ end. A crRNA can include a spacer-repeat sequence with additional inverted repeat sequences, or portion thereof, the further repeat sequence linked at its 3′ end to the 5′ end of a spacer-repeat sequence, thereby forming a “repeat-spacer-repeat sequence.” In still further embodiments, a repeat-spacer-repeat sequence may be linked at the 3′ end to at least one to up to about six further spacer-repeat sequences (e.g., 1, 2, 3, 4, 5, 6 or more additional consecutive spacer-repeat sequences). In such embodiments, each of the at least one up to six Attorney Docket No.29539-0809WO1 additional consecutive spacer-repeat sequences, each having a 5′ end and a 3′ end, are linked at the 3′ end to the 5′ end of the next spacer-repeat sequence (e.g., a first spacer-repeat sequence linked at the 3′ end to a second spacer-repeat sequence) and so on, to form, for example, a repeat-spacer-repeat-spacer-repeat with up to 6 spacer sequences alternating with up to 8 repeat sequences. A “spacer sequence” as used herein is a nucleotide sequence that is complementary to a target DNA (e.g., a virulence gene of a Shigella pathogen) in the genome (the bacterial chromosome and / or any extrachromosomal plasmids) of a target bacterium (e.g., a bacterium of the genus Shigella). A spacer sequence can be about 17 nucleotides to about 50 nucleotides in length. For example, a nucleotide sequence of the spacer sequence can be from about 17 nucleotides to about 50 nucleotides in length for a crRNA (e.g., for a crRNA intended for use in a Type II CRISPR-Cas system) (e.g., from about 29 to about 43, about 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). In some embodiments, a nucleotide sequence of the spacer sequence can be about from about 17 to about 50 nucleotides, from about 20 to about 40 nucleotides, or from about 25 to about 35 nucleotides. In some embodiments, a nucleotide sequence of the spacer sequence can be at least about 17 nucleotides, at least about 20 nucleotides, at least about 25 nucleotides, at least about 30 nucleotides, or at least about 35 nucleotides. In some embodiments, a nucleotide sequence of the spacer sequence can be less than about 50 nucleotides, less than about 45 nucleotides, less than about 40 nucleotides, or less than about 35 nucleotides. The spacer sequence can be fully complementary or substantially complementary (e.g., at least about 80% complementary (e.g., about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%)) to a target DNA (e.g., a virulence gene of a Shigella pathogen) in the genome (the bacterial chromosome and / or any extrachromosomal plasmids) of a target bacterium. Thus, in some embodiments, the spacer sequence can have zero, one, two, three, four, five, or six mismatches as compared to the target DNA (e.g., a virulence gene of a Shigella pathogen). Mismatches can be contiguous or noncontiguous. In some embodiments, the spacer sequence can have 80% identity to a target DNA (e.g., 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a virulence gene of a Shigella pathogen). In representative embodiments, the spacer sequence has 100% complementarity to the target DNA (e.g., a virulence gene of a Shigella pathogen). Attorney Docket No.29539-0809WO1 Exemplary target DNAs include Shigella virulence factors. For example, Shigella virulence factors can include, without limitation, invasion plasmid antigen H (ipaH4; NCBI Reference Sequence: WP_011110595.1), membrane expression of invasion plasmid antigen H (mxiH; NCBI Reference Sequence: WP_032327164.1 or NP_858270.1), membrane expression of invasion plasmid antigen D (mxiD; NCBI Reference Sequence: WP_046891849.1 or NP_858278.1), virB (NCBI Reference Sequence: WP_162511514.1 or NP_858256.1), iutA (NCBI Reference Sequence: WP_011069568.1), and sitA (NCBI Reference Sequence: WP_000555620.1). A target nucleotide sequence or target DNA for use with a Type I and Type II CRISPR system is located adjacent to or flanked by a PAM (protospacer adjacent motif). While PAMs are often specific to the particular Type I or Type II CRISPR-Cas system, a PAM sequence can be determined by those skilled in the art through established experimental and computational approaches. Thus, for example, experimental approaches include targeting a sequence flanked by all possible nucleotides sequences and identifying sequence members that do not undergo targeting, such as through the transformation of target plasmid DNA (Esvelt et al.2013. Nat. Methods 10:1116-1121; Jiang et al.2013. Nat. Biotechnol.31:233-239). In some aspects, a computational approach can include performing BLAST searches of natural spacers to identify the original target DNA sequences in bacteriophages or plasmids and aligning these sequences to determine conserved sequences adjacent to the target sequence (Briner and Barrangou.2014. Appl. Environ. Microbiol.80:994-1001; Mojica et al.2009. Microbiology 155:733-740). As used herein “sequence identity” refers to the extent to which two optimally aligned polynucleotide or peptide sequences are invariant throughout a window of alignment of components, e.g., nucleotides or amino acids. “Identity” can be readily calculated by known methods including, but not limited to, those described in: Computational Molecular Biology (Lesk, A. M., ed.) Oxford University Press, New York (1988); Biocomputing: Informatics and Genome Projects (Smith, D. W., ed.) Academic Press, New York (1993); Computer Analysis of Sequence Data, Part I (Griffin, A. M., and Griffin, H. G., eds.) Humana Press, New Jersey (1994); Sequence Analysis in Molecular Biology (von Heinje, G., ed.) Academic Press (1987); and Sequence Analysis Primer (Gribskov, M. and Devereux, J., eds.) Stockton Press, New York (1991). For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated if necessary, and sequence algorithm program parameters are designated. The Attorney Docket No.29539-0809WO1 sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Optimal alignment of sequences for aligning a comparison window are well known to those skilled in the art and may be conducted by tools such as the local homology algorithm of Smith and Waterman, the homology alignment algorithm of Needleman and Wunsch, the search for similarity method of Pearson and Lipman, and optionally by computerized implementations of these algorithms such as GAP, BESTFIT, FASTA, and TFASTA available as part of the GCG® Wisconsin Package® (Accelrys Inc., San Diego, Calif.). An “identity fraction” for aligned segments of a test sequence and a reference sequence is the number of identical components which are shared by the two aligned sequences divided by the total number of components in the reference sequence segment, i.e., the entire reference sequence or a smaller defined part of the reference sequence. Percent sequence identity is represented as the identity fraction multiplied by 100. The comparison of one or more polynucleotide sequences may be to a full-length polynucleotide sequence or a portion thereof, or to a longer polynucleotide sequence. For purposes of this invention “percent identity” may also be determined using BLASTX version 2.0 for translated nucleotide sequences and BLASTN version 2.0 for polynucleotide sequences. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length (W) within the query sequence, which either match or satisfy some positive-valued threshold score (T) when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., 1990). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when the cumulative alignment score falls off by the quantity X from its maximum achieved value, the cumulative score goes to zero or below due to the accumulation of one or more negative- scoring residue alignments, or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. For the avoidance of confusion, unless otherwise specified, identity is determined using the BLASTN Attorney Docket No.29539-0809WO1 program for nucleotide sequences with defaults of a wordlength (W) of 11, an expectation (E) of 10, a cutoff of 100, M=5, N=−4, and a comparison of both strands. For amino acid sequences, the BLASTP program is used with defaults of a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89: 10915 (1989)). In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90: 5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a test nucleic acid sequence is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleotide sequence to the reference nucleotide sequence is less than about 0.1 to less than about 0.001. Thus, in some embodiments of the invention, the smallest sum probability in a comparison of the test nucleotide sequence to the reference nucleotide sequence is less than about 0.001. Trans-activating CRISPR RNA (tracrRNA) In some cases, any of the phagemids described herein can also include a tracrRNA for a Type II CRISPR-Cas system. Sequences for tracrRNAs are known in the art. Tail Fibers In some optional embodiments provided here, are recombinant phagemids that further include one or more nucleotide sequence(s) encoding a bacteriophage tail fiber protein (also referred to as a tail fiber) or variants or homologs thereof. Tail fibers facilitate reversible and specific recognition and adsorption to target bacteria. Tail fibers are found at the distal end of a bacteriophage tail, and mediate bacteriophage binding to a specific receptor (e.g., receptor protein) present on the cell surface of the target bacterium. In contrast to antibiotics, which target a broad spectrum of bacterial strains, most bacteriophages infect a limited range of bacteria because bacterial host recognition requires a specific interaction of the bacteriophage tail fibers with the corresponding bacterial host receptor. This high specificity is considered an advantage, as phages kill the targeted bacterial pathogens without harming unrecognized bacteria. Therefore, the inclusion of one or more specific tail fiber(s) or variants thereof in the recombinant phagemids disclosed herein can facilitate killing specific bacterial species, such Attorney Docket No.29539-0809WO1 a species of Shigella. The nucleotide sequences encoding one or more tail fiber(s) or variants thereof are from a bacteriophage that can infect a strain of Shigella. Homologs of any of the tail fibers disclosed herein can facilitate infection of a strain of Shigella. Any of the recombinant phagemids disclosed herein can include one or more nucleotide sequence(s) encoding any tail fibers or variants or homologs thereof that bind to a specific receptor present on the surface of a Shigella bacterial species. Exemplary nucleotide sequences encoding tail fibers can have the nucleotide sequence FDI22 ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33), or homologs or variants thereof. For example, a variant of a nucleotide sequence encoding tail fiber having the nucleotide sequence ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33) can have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to SEQ ID NO: 33. Tail fibers or variants or homologs thereof can have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to Φ2457T (e.g., ORF52 (SEQ ID NO: 38) or can have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to ORF46 (SEQ ID NO: 39)), or any other Shigella- targeting bacteriophage. Exemplary tail fiber sequences include those having NCBI Reference Sequence. YP_009609269.1, YP_009609263.1, YP_009112960.1, YP_009112954.1, YP_009787740.1, YP_009787746.1, YP_009804093.1, YP_009804087.1, QGF20004.1, QGF20010.1, QGF19876.1, QGF19882.1, YP_009792870.1, and YP_009792864.1. When a recombinant phagemid is inside of a bacteriophage head, the tail fiber that is encoded by a specific one or more nucleotide sequence(s) and is on the tail of the bacteriophage can be a native tail fiber. For example, a native tail fiber is derived from a bacteriophage that is the same as the bacteriophage that encodes the nucleotide sequence for the bacteriophage head proteins and that lacks genetic modifications. In some examples, a native tail fiber is a tail fiber of Φ2457T. For example, a native tail fiber can be encoded by phi2457T ORF52 (SEQ ID NO: 38). A native tail fiber can also be encoded by phi2457T ORF46 (SEQ ID NO: 39). Alternatively, the tail fiber can be a non-native tail fiber or variant thereof. A non- native tail fiber can be derived from a bacteriophage that is different from the bacteriophage that encodes the nucleotide sequence for the bacteriophage head proteins and that lacks genetic modifications. Exemplary non-native tail fibers can be encoded by nucleotide sequence FDI22 ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33), or homologs or variants thereof. For example, non-native tail fibers of the present Attorney Docket No.29539-0809WO1 disclosure can be encoded by SEQ ID NO: 33 (FDI22 ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002) or nucleotide sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to SEQ ID NO: 33. Non-native tail fibers can also be variants of native tail fibers (i.e., a tail fiber that has mutations as compared to the native tail fiber). For example, a non-native tail fiber can be a variant of a tail fiber of Φ2457T (i.e., a tail fiber that has mutations as compared to native tail fiber of Φ2457T). Thus, in some examples, non-native tail fibers can be encoded by nucleotide sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to nucleotide sequences encoding any of the tail fibers of Φ2457T or any other Shigella-targeting bacteriophage. For example, non-native tail fibers of the present disclosure can be encoded by nucleotide sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to phi2457T ORF52 (SEQ ID NO: 38). Non-native tail fibers of the present disclosure can also be encoded by nucleotide sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to phi2457T ORF46 (SEQ ID NO: 39)). Exemplary non- native tail fiber sequences can include those having NCBI Reference Sequence. YP_009609269.1, YP_009609263.1, YP_009112960.1, YP_009112954.1, YP_009787740.1, YP_009787746.1, YP_009804093.1, YP_009804087.1, QGF20004.1, QGF20010.1, QGF19876.1, QGF19882.1, YP_009792870.1, and YP_009792864.1. Packaging (Pac) Site Unlike some plasmids, recombinant phagemids can also be packaged into the capsid (also referred to as a head) of a bacteriophage because recombinant phagemids can contain a genetic sequence called a packaging (pac) site that facilitates packaging the nucleic acid containing the pac site into the bacteriophage capsid. The pac site is specific for each type of bacteriophage. Any pac site that facilitates packaging of the phagemid into the desired helper bacteriophage can be used. Exemplary nucleotide sequences encoding a pac site that can be used in the phagemids described herein include SEQ ID NO: 34. In some cases, a pac site can include nucleotide sequences having 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 34 or 40-42, and / or nucleotide sequences having between 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotide substitutions compared to SEQ ID NO: 34 or 40-42. Attorney Docket No.29539-0809WO1 Origin of Replication Recombinant phagemids can also include an origin of replication derived from a plasmid, e.g., to facilitate replication in a bacterial cell and an origin of replication derived from bacteriophage that facilitates replication in a bacterial cell during helper phage infection and / or increases transduction efficiency. Exemplary nucleotide sequences encoding an origin of replication derived from bacteriophage that facilitates replication in a bacterial cell (also referred to a bacteriophage origin of replication) can include SEQ ID NO: 35. In some cases, a bacteriophage origin of replication can include nucleotide sequences having 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 35, and / or nucleotide sequences having between 0-10 nucleotide substitutions compared to SEQ ID NO: 35. Bacteriophage origins of replication can also include predicted origins or replication based, for example, on GC skew analysis. Exemplary nucleotide sequences encoding an origin of replication derived from a plasmid that facilitates replication in a bacterial cell (also referred to a plasmid origin of replication) can include SEQ ID NO: 36, colE1 (SEQ ID NO: 36), pMB1, pBR322, R6K, pSC101, and p15A (SEQ ID NO: 55). In addition, any plasmid origin of replication that facilitates replication of the phagemid in a bacterial cell and / or increases transduction efficiency to a bacterial cell, such as a donor cell as defined herein, can be used. In some cases, a plasmid origin of replication can include nucleotide sequences having 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO: 36, and / or nucleotide sequences having between 0-10 nucleotide substitutions compared to SEQ ID NO: 36. Genetically Modified Bacteriophages (Helper Bacteriophage) Also disclosed herein are genetically modified bacteriophages (referred to as helper bacteriophages or helper phages) that can help package any of the recombinant phagemids described herein into a bacteriophage particle (e.g., a chimeric bacteriophage particle). The genetically modified bacteriophages disclosed herein contain mutations in bacteriophage proteins that are required for replication and lysis of a host cell (e.g., a Shigella cell). Therefore, the genetically modified bacteriophages disclosed herein cannot replicate in an unmodified Shigella cell (i.e., cannot use an unmodified Shigella cell as a host cell). Rather, the genetically modified bacteriophages disclosed herein can only infect a host cell that includes mutations to complement and / or suppress the mutation in the mutated bacteriophage proteins that are required for replication and lysis of a host cell. This severely limits the host range of the genetically modified bacteriophage and facilitates biocontainment and safety. Attorney Docket No.29539-0809WO1 Exemplary bacteriophage proteins that are required for replication and lysis of a host cell (e.g., a Shigella cell). For example, proteins that are required for replication and lysis include ORFs 53-57 (DNA replication) and ORFs 64-66 (lysis) from Φ2457T or equivalent homologs thereof in phages that are part of the same family as Φ2457T (e.g., phages within the Tunavirus genus). Sequences of ORFs 53-57 (DNA replication) and ORFs 64-66 (lysis) and phages similar to Φ2457T are provided in Table 3 below. A genetically modified bacteriophage can include one, two, or more mutated nucleotide sequences encoding a gene needed for replication and / or lysis. In a specific embodiment, the mutated proteins are: DnaA or homologs thereof (e.g., ORF54 of the 2457T bacteriophage that targets Shigella (also referred to as Φ2457T)), DNA helicase or homologs thereof (e.g., ORF55 of Φ2457T), and lysin or homologs thereof (e.g., ORF65 of Φ2457T). A genetically modified bacteriophage can include one, two, or more mutated nucleotide sequences encoding a DnaA protein or a homolog thereof, a mutated nucleotide sequence encoding a DNA helicase or a homolog thereof, and a mutated nucleotide sequence encoding a lysin or a homolog thereof. A mutated nucleotide sequence encoding a DnaA or homolog thereof, a DNA helicase or homolog thereof, or a lysin or homolog thereof can result in a non-functional protein (e.g., a non-functional DnaA or non- functional homolog thereof, a non-functional DNA helicase or non-functional homolog thereof, or a non-functional lysin or non-functional homolog). In some cases, a mutated nucleotide sequence encoding a DnaA or homolog thereof, a DNA helicase or homolog thereof, or a lysin or homolog thereof can result in a truncated protein (e.g., a truncated DnaA or truncated homolog thereof, a truncated DNA helicase or truncated homolog thereof, or a truncated lysin or truncated homolog). Exemplary mutations that could result in a truncated protein include, but are not limited to, an amber mutation. An amber mutation results from a nucleotide substitution that converts a codon encoding an amino acid into a UAG codon, which signals the termination of the translation of an amino acid chain. For example, a genetically modified bacteriophage can include one, two, or all three of a mutated nucleotide sequence encoding a DnaA protein or a homolog thereof, a mutated nucleotide sequence encoding a DNA helicase or a homolog thereof, and a mutated nucleotide sequence encoding a lysin or a homolog thereof, where each mutated nucleotide sequence includes one or more amber mutation(s). In some cases, the genetically modified bacteriophage containing one or more amber mutation(s) cannot replicate in host cells (e.g., Shigella cells) lacking amber suppressor transfer RNAs. In some Attorney Docket No.29539-0809WO1 cases, the genetically modified bacteriophage containing amber mutations only replicates in host cells (e.g., Shigella cells) including amber suppressor transfer RNAs. Genetically modified bacteriophages can also include one or more genetic modification(s) to nucleotide sequences encoding tail fiber proteins. For example, the nucleotide sequences encoding tail fiber proteins can be deleted or truncated, e.g., at least 70% truncated, such that a functional tail fiber protein cannot be produced. Exemplary nucleotide sequences encoding tail fiber proteins that can be deleted or truncated include Φ2457T ORF46 (SEQ ID NO: 39) and Φ2457T ORF52 (SEQ ID NO: 38). Thus, helper bacteriophages described herein can include bacteriophages where the nucleotide sequences encoding the tail fibers are deleted. Such helper phages (e.g., where nucleotide sequences encoding the tail fibers are deleted) can be used for assembling exogenous and / or non-native tail fibers (e.g., any of the non-native tail fibers described herein) onto bacteriophage particles during donor infection, and for producing the chimeric bacteriophage particles of the present disclosure. For example, for obtaining the chimeric bacteriophage particles of the present disclosure, phi2457Tam3ΔORF52 helper phages (phi2457T ORF54am ORF55am ORF65am deltaORF52::lacZ) can be used, where lacZ is inserted into the phi2457T ORF52 sequence to delete the tail fibers. Thus, the tail fiber homologs or variants provided in trans (complementation) can assemble onto phage particles during donor infection using these helper phages. To help package any of the recombinant phagemids described herein into a bacteriophage particle, the helper bacteriophage must recognize and infect an RGN donor cell (e.g., a genetically modified Shigella cell). Therefore, the tail fiber proteins on the tail of the helper bacteriophage must recognize a receptor (e.g., receptor protein) on the RGN donor cell (e.g., a genetically modified Shigella cell) to successfully infect the RGN donor cell. Genetically Modified Donor Cells (also referred to as RGN Donor Cells) and Methods of Making the Same Also disclosed herein are genetically modified bacterial cells (which can also be referred to as RGN donor cells or donor cells) (e.g., genetically modified Shigella cells) that contain one or more genetic modification(s) that complement and / or suppress a mutation in the mutated bacteriophage, where the mutation (e.g., an amber mutation) in the mutated bacteriophage is in a nucleotide sequence encoding a protein that is required for replication and lysis of a host cell. The genetically modified bacterial cells (e.g., genetically modified Shigella cells) can contain one or more nucleotide sequences encoding one or more amber Attorney Docket No.29539-0809WO1 suppressor transfer RNA(s) (tRNA(s)). Exemplary amber suppressor tRNA can include, and are not limited to, a supF amber suppressor tRNA. For example, a supF amber suppressor tRNA can be encoded by a nucleotide sequence having the sequence of SEQ ID NO: 37, can be encoded by a nucleotide sequence having 80%, 85%, 90%, 95% or more sequence identity to SEQ ID NO: 37, or can be encoded by a nucleotide sequence having 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mutations compared to the nucleotide sequence set forth in SEQ ID NO: 37. Any of the genetically modified bacterial cells (e.g., genetically modified Shigella cells) also express a bacterial host receptor on their outer membrane. Helper bacteriophages bind to specific bacterial host receptors to help identify Shigella bacteria that the helper bacteriophages can infect. Bacterial host receptors can include any bacterial surface molecule, including but not limited to, a protein, glycan, or lipid present on the bacterial surface. In some cases, the bacterial host receptor can bind to a tail fiber of a helper bacteriophage that can infect Shigella, where the helper bacteriophage that can infect Shigella is not a Φ2457T bacteriophage. In some cases, the bacterial host receptor can bind to a tail fiber of a helper bacteriophage that can infect Shigella, where the helper bacteriophage that can infect Shigella is a Φ2457T bacteriophage. For example, a nucleotide sequence encoding a bacterial host receptor that can bind to a tail fiber of a helper bacteriophage capable of infecting Shigella encodes a bacterial host receptor (e.g., receptor protein) that can bind to a tail fiber that is encoded by Φ2457T ORF46 (SEQ ID NO: 39) and Φ2457T ORF52 (SEQ ID NO: 38). Any of the nucleotide sequences encoding one or more amber suppressor tRNAs can be located on a bacterial vector or can be integrated into a bacterial genome (e.g., integrated into a Shigella genome). The vector can be an exogenously added vector. Regardless of the location of the nucleotide sequence encoding the one or more amber suppressor tRNAs, any of the nucleotide sequences encoding the one or more amber suppressor tRNAs can be operably linked to a promoter (e.g., a constitutive promoter, an inducible promoter, or an artificial promoter). Promoters useful with this invention can include any promoter functional in bacteria. Exemplary promoters include useful with this invention include promoters functional in bacteria. A promoter useful with bacteria can include, but is not limited to, L- arabinose inducible (araBAD, PBAD) promoter, any lac promoter, L-rhamnose inducible (rhaPBAD) promoter, T7 RNA polymerase promoter, trc promoter, tac promoter, lambda phage promoter (pL, pL-9G-50), anhydrotetracycline-inducible (tetA) promoter, trp, lpp, phoA, recA, proU, cst-I, cadA, nar, lpp-lac, cspA, T7-lac operator, T3-lac operator, T4 gene 32, T5-lac operator, nprM-lac operator, Vhb, Protein A, corynebacterial-E. coli like promoters, thr, horn, diphtheria toxin promoter, sigA, sigB, nusG, SoxS, katb, α-amylase Attorney Docket No.29539-0809WO1 (Parry), Ptms, P43 (comprised of two overlapping RNA polymerase σ factor recognition sites, σA, σB) Ptms, P43, rplK-rplA, ferredoxin promoter, xylose promoter, a tetracycline inducible promoter (PLtetO-1), any native Shigella promoter. (See, K. Terpe Appl. Microbiol, Biotechnol.72:211-222 (2006); Hannig et al. Trends in Biotechnology 16:54-60 (1998); Srivastava, Protein Expr Purif 40:221-229 (2005); and Citorik et al. Nature Biotechnol. 2014). In some cases, the promoter is or a tetracycline inducible promoter (PLtetO-1). In some cases, the promoter is a Φ2457T ORF52 promoter. In some cases, the promoter is a Φ2457T ORF46 promoter. The choice of promoter will vary depending on the quantitative, temporal and spatial requirements for expression, and also depending on the host cell to be transformed. Promoters for many different organisms are well known in the art. Based on the extensive knowledge present in the art, the appropriate promoter can be selected for the particular host organism of interest. Thus, for example, much is known about promoters upstream of highly constitutively expressed genes in model organisms and such knowledge can be readily accessed and implemented in other systems as appropriate. In some embodiments, inducible promoters can be used. Thus, for example, chemical- regulated promoters can be used to modulate the expression of a gene in an organism through the application of an exogenous chemical regulator. Regulation of the expression of nucleotide sequences of the invention via promoters that are chemically regulated enables the RNAs and / or the polypeptides of the invention to be synthesized only when, for example, an organism is treated with the inducing chemicals. Depending upon the objective, the promoter may be a chemical-inducible promoter, where application of a chemical induces gene expression, or a chemical-repressible promoter, where application of the chemical represses gene expression. Any of the one or more genetic modification(s) that suppress and / or complement a mutation in the mutated bacteriophage (e.g., an amber suppressor tRNA), where the mutation in the mutated bacteriophage (e.g., an amber mutation) is in a nucleotide sequence encoding a protein that is required for infection, replication and lysis of a host cell that is operably linked to a promoter can be genetically engineered on any suitable vector. The vector can be an exogenously added vector. An exemplary method of making is described in Example 1. Any vector described herein containing any of the one more genetic modification(s) that suppress and / or complement a mutation in the mutated bacteriophage (e.g., an amber suppressor tRNA) can be incorporated (e.g, transformed or transduced) into any suitable bacterial cell (e.g., a Shigella bacterial cell) using any appropriate method. General methods of vector Attorney Docket No.29539-0809WO1 genetic engineering and transduction are known in the art. See, for example, Citorik et al. Nature Biotechnol.2014). A genetically modified bacterial cell (e.g., a genetically modified Shigella cell) can also include any of the recombinant phagemids described herein. Any of the genetically modified bacterial cells described herein can also include a variant of the native phi2457T tail fibers (e.g., a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to any of the tail fibers of Φ2457T (e.g., Φ2457T ORF52 (SEQ ID NO: 38) or Φ2457T ORF46 (SEQ ID NO: 39))), a non-native tail fiber, or variants thereof. For example, a variant of the native phi2457T tail fiber, a non-native tail fiber, or variant thereof can be provided by the genetically modified bacterial cell (e.g., the genetically modified Shigella cell, such as a donor cell). For example, a variant of the native phi2457T tail fiber, the non-native tail fiber, or variant thereof provided by the genetically modified bacterial cell can be provided on a different plasmid or vector, or inserted into the genome of the genetically modified bacterial cell. Exemplary nucleotide sequences encoding tail fibers can have the nucleotide sequence of FDI22 ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33), or homologs or variants thereof. For example, a variant of a nucleotide sequence encoding tail fiber having the nucleotide sequence of ORF14 of the Shigella-targeting bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33) can have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to SEQ ID NO: 33. In addition, tail fibers or variants or homologs thereof can have 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to any of the tail fibers of Φ2457T (e.g., ORF52 (SEQ ID NO: 38) or ORF46 (SEQ ID NO: 39)), or any other Shigella-targeting bacteriophage. Exemplary tail fiber sequences include those having NCBI Reference Sequence. YP_009609269.1, YP_009609263.1, YP_009112960.1, YP_009112954.1, YP_009787740.1, YP_009787746.1, YP_009804093.1, YP_009804087.1, QGF20004.1, QGF20010.1, QGF19876.1, QGF19882.1, YP_009792870.1, and YP_009792864.1. A genetically modified bacterial cell (e.g., a genetically modified Shigella cell) can be of any species of Shigella. For example, a genetically modified Shigella cell can be a genetically modified Shigella flexneri cell, a genetically modified S. dysenteriae cell, a genetically modified S. boydii cell, or a genetically modified S. sonnei cell. Attorney Docket No.29539-0809WO1 Chimeric Bacteriophage Particles (ΦRGN transducing particle) and Methods of Making the Same Provided herein are chimeric bacteriophage particles (also referred to as ΦRGN transducing particles) containing recombinant phagemids that facilitate targeted CRISPR- based Shigella bacteria-killing mechanisms within a bacteriophage scaffold (e.g., bacteriophage head, tail, and tail fiber(s)) derived from a genetically modified bacteriophage (helper bacteriophage). Chimeric bacteriophage particles can include any of the recombinant phagemids disclosed herein. For example, a chimeric bacteriophage particle can include (e.g., contain within the bacteriophage head) any of the recombinant phagemids disclosed herein. Also, a chimeric bacteriophage particle can include one or more tail fiber(s) of a non-native tail fiber variant (e.g., a tail fiber that is derived from a bacteriophage that is different from the bacteriophage that encodes the nucleotide sequence for the bacteriophage head proteins of the chimeric bacteriophage particle and that lacks genetic modifications). For example, a chimeric bacteriophage particle includes a) a recombinant phagemid that includes i) a first nucleotide sequence encoding any of the crRNAs described herein, ii) a nucleotide sequence encoding any of the cas nucleases described herein, iii) a variant of a nucleotide sequence encoding any of the native phi2457T tail fibers, a nucleotide sequence encoding non-native tail fibers, or variants thereof described herein, iv) a nucleotide sequence having any of the pac sites described herein, and v) a nucleotide sequence having any of the bacteriophage origin of replications described herein; and b) one or more of any of the tail fiber(s) of a variant of the native phi2457T tail fibers, non-native tail fibers, or variants thereof described herein. Any of the chimeric bacteriophage particles described herein can also include bacteriophage head proteins and tail proteins encoded by the helper phages. The bacteriophage head and bacteriophage tail proteins generate the bacteriophage scaffold of the chimeric bacteriophage particles. The phagemid is packaged into the bacteriophage head instead of the native bacteriophage genome, and the non-native tail fiber(s) or tail fiber variants (e.g., variants of the native phi2457T tail fibers or variants of non-native tail fibers) are assembled onto the bacteriophage tail proteins. Any of the chimeric bacteriophage particles described herein can transduce any of the recombinant phagemids described herein into any strain of Shigella described herein. For example, any of the chimeric bacteriophage particles described herein can transduce a recombinant phagemid into a strain of S. dysenteriae, S. flexneri, S. boydii, or S. sonnei. Transduction can be determined by a transducing particle titer assay, such as the transducing Attorney Docket No.29539-0809WO1 particle titer assay described in Example 1. For example, a plurality of chimeric bacteriophage particles can have up to 100% transduction efficiency (e.g., from about 0.01% to about 100%, from about 0.1% to about 100%, from about 1% to about 100%, from about 10% to about 100%, from about 15% to about 75%, from about 20% to about 40%, or from about 30% to about 80%). Also, any of the chimeric bacteriophage particles described herein can kill any of the strain of Shigella described herein. For example, any of the chimeric bacteriophage particles described herein can kill a strain of S. dysenteriae, S. flexneri, S. boydii, or S. sonnei. Efficacy of targeted-Shigella killing can be determined as described in Example 1. For example, a broth infection assay can be used to determine the efficacy of targeted-Shigella killing of any of the chimeric bacteriophage particles described herein. In some cases, the number of Shigella cells was reduced by about 5x10-3-fold (e.g., from about 3 x 103-fold to about 8 x 103-fold, from about 3 x 103-fold to about 7 x 103-fold, or from about 4.7 x 103-fold to about 6.6 x 103-fold). In some cases, a chimeric virion particle causes the death of a bacterial cell of a strain of Shigella. In some cases, infection of a bacterial cell of a strain of Shigella with a chimeric virion particle results in cell death. In some cases, infection of a bacterial cell of a strain of Shigella with a chimeric virion particle does not cause cell lysis via bacteriophage lysis of the bacterial cell. Without being bound by a single theory, infection of a bacterial cell of a strain of Shigella by any of the chimeric virion particles described herein can result in double stranded breaks in Shigella DNA in target DNA (e.g., DNA that is complementary to a spacer sequence of a recombinant phagemid, such as virulence factors). In some cases, a virulence plasmid of a strain of Shigella is targeted by the encoded CRISPR-Cas system and is damaged such that virulence factors can no longer be produced by the Shigella cell. In some cases, a virulence plasmid of a strain of Shigella is targeted by the encoded CRISPR-Cas system and is destroyed. In some cases, sufficient DNA damage of the bacterial cell of the strain of Shigella occurs that the bacterial cell lyses. Once a genome of any of the genetically modified bacteriophages and any of the recombinant phagemids described herein are both inside of the genetically modified bacterial cell (e.g., the genetically modified Shigella cell, such as a donor cell), a chimeric bacteriophage particle (or particles) can be produced. For example, the genome of the genetically modified bacteriophages contains the genetic instructions to produce and assemble all of the components of the chimeric bacteriophage particle (e.g., head proteins, assembly proteins, tail proteins, etc.), except for the variant of the native phi2457T tail fibers, Attorney Docket No.29539-0809WO1 the non-native tail fibers, or variants thereof. In some cases, the recombinant phagemid contains the CRISPR-Cas system and the nucleotide sequence for the variant of the native phi2457T tail fibers, the non-native tail fibers, or variants thereof. In other cases, the nucleotide sequence of the variant of the native phi2457T tail fibers, the non-native tail fibers, or variants thereof is provided by the genetically modified bacterial cell (e.g., the genetically modified Shigella cell, such as a donor cell). For example, the nucleotide sequence of the variant of the native phi2457T tail fibers, the non-native tail fibers, or variants thereof are provided by the genetically modified bacterial cell can be provided on a different plasmid or vector, or inserted into the genome of the genetically modified bacterial cell. The chimeric bacteriophage particle uses the structure of the genetically modified bacteriophage. However, in at least a subsection of the chimeric bacteriophage particles, the phagemid is packaged into the chimeric bacteriophage particle head instead of the genome of genetically modified bacteriophage, and the non-native tail fibers or variants thereof are assembled onto the tail instead of the native tail fibers of the genetically modified bacteriophage. The resulting product is any of the chimeric bacteriophage particles described herein. For example, for obtaining the chimeric bacteriophage particles of the present disclosure, phi2457Tam3ΔORF52 helper phages (phi2457T ORF54am ORF55am ORF65am deltaORF52::lacZ) can be used, where lacZ is inserted into the phi2457T ORF52 sequence to delete the tail fibers. The phi2457Tam3ΔORF52 helper phages can be used for assembling exogenous and / or non-native tail fibers (e.g., any of the non-native tail fibers described herein) onto bacteriophage particles during donor infection, thus producing the chimeric bacteriophage particles of the present disclosure. Chimeric Bacteriophage Particle Library and Methods of Making the Same Also disclosed herein are chimeric bacteriophage particle libraries. Chimeric bacteriophage particle libraries are used to determine which of a variety of non-native tail fibers can infect a specific strain of Shigella. For example, a chimeric bacteriophage particle library includes a plurality (e.g., two or more) of unique chimeric bacteriophage particles, where each of the unique chimeric bacteriophage particles, which can be any of the chimeric bacteriophage particles described herein, includes a unique nucleotide sequence encoding a unique non-native tail fiber. A chimeric bacteriophage particle library can be contacted to a target strain of Shigella, and the unique chimeric bacteriophage particle that successfully bind to or infects the target strain is identified. An exemplary method of identifying which Attorney Docket No.29539-0809WO1 chimeric bacteriophage particle bound to or infected the target strain of Shigella is described in Example 1. Once two or more unique recombinant phagemids are introduced in the genetically modified bacterial cell populations (e.g., a plurality of the genetically modified Shigella donor cell), a chimeric bacteriophage particle (or particles) can be produced; each bacterial cell will only include a single unique phagemid. For example, the genome of the genetically modified bacteriophages contains the genetic instructions to produce and assemble all of the components of the chimeric bacteriophage particle (e.g., head proteins, assembly proteins, tail proteins, etc.), except for the variant of the native phi2457T tail fibers, the non-native tail fibers, or variants thereof. The recombinant phagemid contains the CRISPR-Cas system and the nucleotide sequence for the non-native tail fibers or variants thereof. The chimeric bacteriophage particle uses the structure of the genetically modified bacteriophage. However, in at least a subsection of the chimeric bacteriophage particles, the recombinant phagemid is packaged into the chimeric bacteriophage particle head instead of the genome of genetically modified bacteriophage, and the non-native tail fibers or variants thereof are assembled onto the tail instead of the native tail fibers of the genetically modified bacteriophage. The resulting product is any of the chimeric bacteriophage particles described herein. An exemplary method of making a chimeric bacteriophage particle library is described in Example 1 and shown in Fig.5A and Fig.5B. System of Genetically Modified Bacteriophages (Helper Bacteriophage) and Genetically Modified Bacterial Cells (Donor Cells) for Use in Making Chimeric Bacteriophage Particles To produce a chimeric bacteriophage particle, a system including any of the genetically modified bacteriophages (helper bacteriophages) disclosed herein and any of the genetically modified bacterial cells disclosed herein (donor cell; e.g., a genetically modified Shigella cell) are used, where the genetically modified bacteriophages include mutations in bacteriophage proteins that are required for infection, replication, and lysis of a host cell (e.g., a Shigella cell) and the genetically modified bacterial cell (e.g., the genetically modified Shigella donor cell) includes i) genetic modifications to suppress and / or complement the mutation in the mutated bacteriophage proteins that are required for infection, replication, and lysis of a host cell, and ii) any of the recombinant phagemids described herein. For example, genetically modified bacteriophages including amber mutations and the genetically modified bacterial cells (e.g., the genetically modified Shigella cells) including amber suppression Attorney Docket No.29539-0809WO1 tRNAs can be used. The genetically modified bacterial cell (e.g., the genetically modified Shigella cells) that includes the mutations that suppress and / or complement the mutation in the mutated bacteriophage proteins also includes any of the recombinant phagemids disclosed herein. For example, a genetically modified bacterial cell (e.g., the genetically modified Shigella cells) that includes the genetic modifications that complement the mutation in the mutated bacteriophage proteins can be transformed to incorporate any of the recombinant phagemids described herein before, concurrently, or after the genetically modified bacteriophages are contacted with the genetically modified bacterial cell (e.g., the genetically modified Shigella cells). To produce a chimeric bacteriophage particle library, a system including any of the genetically modified bacteriophages (helper bacteriophages) described herein and a plurality of any of the genetically modified bacterial cells (donor cells) (e.g., any of the genetically modified Shigella cells) disclosed here are used. The genetically modified bacteriophages include mutations in bacteriophage proteins that are required for infection, replication, and lysis of a host cell (e.g., a Shigella cell). For example, in the genetically modified bacteriophages (helper bacteriophages), nucleotide sequences encoding the tail fibers can be deleted. Such helper bacteriophages (e.g., where nucleotide sequences encoding the tail fibers are deleted) can be used for assembling non-native tail fibers (e.g., any of the non-native tail fibers described herein) onto bacteriophage particles during donor infection, thus producing the chimeric bacteriophage particles of the present disclosure. Preferably, for obtaining chimeric bacteriophage particles of the present disclosure, phi2457Tam3ΔORF52 helper phages (phi2457T ORF54am ORF55am ORF65am deltaORF52::lacZ) can be used, where lacZ is inserted into the phi2457T ORF52 sequence to delete the tail fibers. Thus, tail fiber homologs or variants provided in trans (complementation) can assemble onto phage particles during donor infection using these helper phages. The plurality of the genetically modified bacterial cells (e.g., the genetically modified Shigella cells) includes two or more unique genetically modified bacterial cells, each of which includes i) mutations to suppress and / or complement the mutation in the mutated bacteriophage proteins that are required for infection, replication, and lysis of a host cell, and ii) a unique recombinant phagemid of any of the recombinant phagemids disclosed herein. For example, genetically modified bacteriophages including amber mutations and the genetically modified bacterial cells (e.g., the genetically modified Shigella cells) including amber suppression tRNAs can be used. For example, a genetically modified bacterial cell (e.g., the genetically modified Shigella cells) that includes the genetic modifications that complement the mutation in the mutated Attorney Docket No.29539-0809WO1 bacteriophage proteins can be transformed to incorporate any of the recombinant phagemids described herein before, concurrently, or after the genetically modified bacteriophages are contacted with the genetically modified bacterial cell (e.g., the genetically modified Shigella cells). A unique genetically modified bacterial cell can include a recombinant phagemid with a unique non-native tail fiber. Pharmaceutical Compositions Also disclosed herein are pharmaceutical compositions including any of the chimeric bacteriophage particles described herein and a pharmaceutically acceptable carrier. Also disclosed herein are pharmaceutical composition including any of the genetically modified bacteriophage described herein and any of the genetically modified Shigella cell described herein, where the genetically modified Shigella cell includes any of the recombinant phagemids described herein. The term “pharmaceutically acceptable carrier” refers to a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. For drugs administered orally, pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract. Method of Treatment Using Chimeric Bacteriophage Particles Also described herein are methods of treating a Shigella infection. Any appropriate mammal having a Shigella infection can be assessed and / or treated as described herein. Examples of mammals that can have a Shigella infection that can be assessed and / or treated as described herein include, without limitation, humans and non-human primates (e.g., monkeys). For example, a human having a Shigella infection can be assessed and / or treated as described herein. Attorney Docket No.29539-0809WO1 A subject can be identified as having a Shigella infection using any standard Shigella identification method. For example, a sample (e.g., a stool sample) can be obtained from the subject and tested for the presence of Shigella bacterial cells and / or for Shigella toxins using any appropriate laboratory assay (e.g., culturing or genetic analysis). Alternatively, or in addition, a subject can present with Shigella symptoms, including diarrhea and / or bloody diarrhea, stomach pain, stomach cramps, fever, nausea, and / or vomiting. In some cases, a subject was previously identified as having a Shigella infection. In some cases, a mammal (e.g., a human) having a Shigella infection that is assessed as described herein can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) treatments and / or interventions effective to treat the Shigella infection. For example, a mammal (e.g., a human) having a Shigella infection and assessed as described herein can be administered or instructed to self-administer one or more treatments and / or interventions that are selected based, at least in part, on the strain of the Shigella causing the infection. Administering any of the pharmaceutical compositions to a mammal (e.g., a human) identified (or previously identified) as having a Shigella infection can use any appropriate route of administration. For example, the chimeric bacteriophage particles and pharmaceutical compositions described herein can be manufactured in a form suitable for oral, rectal, buccal (e.g., sub-lingual), vaginal, parenteral (e.g., subcutaneous, intramuscular including skeletal muscle, cardiac muscle, diaphragm muscle and smooth muscle, intradermal, intravenous, intraperitoneal), intraarticular, and inhalation administration. In some embodiments, chimeric bacteriophage particles and pharmaceutical compositions described herein is delivered to the site of Shigella infection (e.g., to the gastrointestinal tract). The most suitable route in any given case will depend on the nature and severity of the condition being treated. For oral administration, the chimeric bacteriophage particles and pharmaceutical compositions described herein can be administered in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as elixirs, syrups, and suspensions. The chimeric bacteriophage particles and pharmaceutical compositions described herein can be encapsulated in gelatin capsules together with inactive ingredients and powdered carriers, such as glucose, lactose, sucrose, mannitol, starch, cellulose or cellulose derivatives, magnesium stearate, stearic acid, sodium saccharin, talcum, magnesium carbonate and the like. Examples of additional inactive ingredients that can be added to provide desirable color, taste, stability, buffering capacity, dispersion or other known desirable features are red iron Attorney Docket No.29539-0809WO1 oxide, silica gel, sodium lauryl sulfate, titanium dioxide, edible white ink and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric-coated for selective disintegration in the gastrointestinal tract. Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance. Compositions suitable for buccal (sub-lingual) administration include lozenges comprising a flavored base, usually sucrose and acacia or tragacanth; and pastilles comprising an inert base such as gelatin and glycerin or sucrose and acacia. Compositions suitable for rectal administration are preferably presented as unit dose suppositories. These can be prepared by admixing the host bacteria in one or more conventional solid carriers, for example, cocoa butter, and then shaping the resulting mixture. “Effective amount” as used herein refers to an amount of a chimeric bacteriophage particle and / or pharmaceutical composition thereof that is sufficient to produce a desired effect, which can be a therapeutic and / or beneficial effect. The effective amount will vary with the age, general condition of the subject, the severity of the condition being treated, the particular agent administered, the duration of the treatment, the nature of any concurrent treatment, the pharmaceutically acceptable carrier used, and like factors within the knowledge and expertise of those skilled in the art. In some embodiments, an effective amount of a chimeric bacteriophage particle and / or pharmaceutical composition thereof may be from about 105to about 1015transductant-forming units (e.g., 105-1010, 107-1012, or 1010- 1015). In some embodiments, an effective amount may be an amount that reduces the number of Shigella bacterial cells in a sample (e.g., a stool sample) previously obtained from the mammal (e.g., the human) by about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, and any value or range therein. By the terms “treat,” “treating,” or “treatment,” it is intended that the severity of the subject's condition is reduced or at least partially improved or modified and that some alleviation, mitigation or decrease in at least one clinical symptom is achieved, and / or there is a delay in the progression of the disease or condition, and / or delay of the onset of a disease or illness. With respect to an infection, a disease or a condition, the term refers to, e.g., a decrease in the symptoms or other manifestations of the infection, disease or condition. In some embodiments, treatment provides a reduction in symptoms or other manifestations of Attorney Docket No.29539-0809WO1 the infection, disease or condition by at least about 5% to about 100%, e.g., about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% or more. Further, with respect to an infection, a disease or a condition, the terms “treat,” “treating,” or “treatment of” and the like refer to, e.g., elimination of or a decrease in the presence or amount of a microorganism (e.g., bacteria) in the subject. Thus, by treating the infection, disease, and / or condition in the subject, the infection, disease, and / or condition is ameliorated, alleviated, severity reduced, symptoms reduced and the like as compared to a similar subject not treated with the chimeric constructs of this invention, thereby treating the infection, disease and / or condition. In some embodiments, the treatment of an infection by a bacterium as described herein can be, for example, bactericidal and / or bacteriostatic. Thus, in some embodiments, the presence of a bacterium may be reduced by about 10% to about 100% (e.g., 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or any value or range therein) upon contact with the chimeric construct of the invention of a composition thereof. When treating a mammal (e.g., a human) identified (or previously identified) as having a Shigella infection as described herein, the treatment can be effective to reduce or eliminate one or more symptoms of a Shigella infection as described above. The materials and methods described herein can be used to reduce one or more symptoms of a Shigella infection present within a mammal (e.g., a human) identified (or previously identified) as having a Shigella infection by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 or more percent. When treating a mammal (e.g., a human) identified (or previously identified) as having a Shigella infection as described herein, the treatment can be effective to reduce or eliminate the number of Shigella bacterial cells in a sample (e.g., a stool sample) previously obtained from the mammal (e.g., the human). The materials and methods described herein can be used to reduce the number of Shigella bacterial cells in a sample (e.g., a stool sample) previously obtained from the mammal (e.g., the human) identified (or previously identified) as having a Shigella infection by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95 or more percent. In some embodiments, when treating a mammal (e.g., a human) identified (or previously identified) as having a Shigella infection as described herein, the method also includes administering a second therapeutic agent. For example, the method also includes administering or instructing to self-administer an effective amount of one or more second Attorney Docket No.29539-0809WO1 therapeutic agent(s). Exemplary second therapeutic agents can include an anti-diarrheal and / or a rehydration solution. In some embodiments, the anti-diarrheal includes bismuth subsalicylate. Exemplary anti-diarrheals include, but are not limited to, PEPTO-BISMOL® and KAOPECTATE®. In some embodiments, the rehydration solution is an oral rehydration solution or an intravenous rehydration solution. Exemplary oral rehydration solutions are fluids for oral consumption that contain electrolytes (e.g., potassium and sodium) and carbohydrates (e.g., glucose) to restore fluid and electrolyte balance in the body, and can include, but are not limited to, products sold under the brand names PEDIALYTE® and LIQUID I.V.®. A mammal (e.g., a human) being administered or instructed to self-administer any of the pharmaceutical compositions disclosed herein were previously treated for having a Shigella infection. In some embodiments, a mammal (e.g., a human) being administered or instructed to self-administer any of the pharmaceutical compositions disclosed herein were previously administered one or more second therapeutic agent(s) as described herein. EXAMPLES Example 1: Engineering lytic bacteriophages as novel antimicrobials targeting Shigella flexneri The Shigella flexneri-specific lytic bacteriophage Φ2457T was engineered to package CRISPR-Cas RNA-guided nucleases (RGNs) that target one or more Shigella-specific virulence factors and deliver them to targeted Shigella bacteria. To build this system, a recombinant phagemid-based construct was designed that packaged exogenous plasmids encoding RGNs targeting conserved virulence genes into phage particles for delivery to pathogenic Shigella flexneri bacteria. Helper bacteriophage were engineered with amber (stop codon) mutations in genes required for bacteriophage DNA replication and bacterial host lysis to limit off-target lysis of commensal bacteria and limit the presence of replicative bacteriophages. Donor bacterial cells engineered with RGN phagemids were infected with genetically-engineered Φ2457T helper phages, resulting in Φ2457T bacteriophage particles containing the RGN phagemids (ΦRGNs). Infection of recipient cells with ΦRGN resulted in RGN-mediated killing of Shigella flexneri that contain the one or more Shigella-specific virulence factors. (Fig.1). Attorney Docket No.29539-0809WO1 Optimizing the transduction efficiency of Φ2457T It was hypothesized that Φ2457T, like other T1-like phages, could package foreign DNA into viral particles at low frequency through generalized transduction. Φ2457T helper phages were engineered to package and deliver exogenous DNA. The putative Φ2457T packaging (pac) site was identified through comparative genomics. This pac sequence, along with flanking sequences of increasing length, was integrated into plasmid backbones to generate putative phagemids. To determine if putative pac sites could be packaged into wild- type (WT) Φ2457T particles, the pac-encoding phagemids were transformed into S. flexneri 2457T host cell which were subsequently infected with WT Φ2457T bacteriophage. DNA from progeny phages was purified, and encapsidated DNA was identified through PCR. The pac1 site, plus an additional 200 nt flanking sequence (pac2), increased phagemid packaging efficiency into WT Φ2457T capsids (Fig.2A). Thus, Φ2457T was capable of packaging phagemid DNA. However, phagemid packaging efficiency was low, which resulted in WT, replicative Φ2457T contaminants in donor cell lysates. Thus, phagemid packaging efficiency was increased and replicative phage contamination was eliminated by genetically modifying the Φ2457T helper phages. Amber mutations were introduced to Φ2457T ORF54 (putative dnaA homolog), ORF55 (DNA helicase), and ORF65 (putative lysin), genes required for bacteriophage DNA replication and bacterial host lysis. The resulting Φ2457Tam3 amber mutant phages (also referred to as Φ2457T ORF54am ORF55am ORF65am) were shown with plaque assays to not infect WT S. flexneri cells and could only be propagated in bacteria expressing amber suppressor transfer RNAs (tRNAs; Fig.2B). To test Φ2457Tam3 helper phage transduction efficiency, transducing particle titer assays were used. Briefly, phagemids were transformed into genetically engineered S. flexneri 2457T cells that constitutively express plasmid-encoded amber suppressor tRNAs (donor cells). supF tRNAs are encoded in a plasmid and transformed into S. flexneri cells. The plasmid sequence is provided as SEQ NO.1 (pZA22supF). Briefly, the supF tRNA is cloned under the control of the constitutive PlacO-1 promoter in a plasmid containing a Kanamycin resistance gene and the p15A origin of replication (SEQ ID NO: 55). The donor cells were then infected with Φ2457Tam3 helper phages. WT S. flexneri 2457T were then infected with each donor cell lysate and recipient cells containing phagemids were enumerated following antibiotic selection (Fig.2C). Φ2457Tam3 helper phages were capable of generalized transduction, with inefficient transduction of empty plasmids or plasmids containing random Φ2457T DNA (ORF51). The Φ2457T pac site with 1.2 kb flanking DNA Attorney Docket No.29539-0809WO1 (pac3mut) had highly efficient phagemid transduction; addition of the Φ2457T origin of replication (in ORF55) increased transduction ~2-fold, resulting in transducing particle titers >1x 108transductant forming units (TFU) / mL and a transduction efficiency (transducing particles / infectious particles) up to 26%. Next, one-step growth curves were performed to confirm that Φ2457Tam3 helper phages cannot replicate in WT S. flexneri cells. Briefly, WT and amber suppressor strains of S. flexneri were infected with Φ2457Tam3.1 helper phages at a multiplicity of infection (MOI) of 0.01. Phenotypically, the Φ2457Tam3.1 helper phage (SEQ ID NO: 56) is identical to the Φ2457Tam3 helper phage (SEQ ID NO: 9), but with an additional amber mutation located within ORF55. After five minutes of incubation at 37℃ to allow for phage adsorption, cultures were diluted, and the phage titer was determined at each indicated time point. The logarithmic-scale plaque-forming units (PFU) / mL were plotted at each time point (n=3, +SD). The data, shown in Fig.2D, indicate that Φ2457Tam3.1 helper phages are unable to replicate in wild-type S. flexneri host cells (white) but can replicate as expected in the amber suppressor cells (black). In all, a phagemid-based system for efficient delivery of reprogrammable DNA payloads into S. flexneri was engineered using the genetically engineered Φ2457Tam3 non-replicative, lytic helper phages. Constructing the RGN phagemid library To create the RGN phagemid, the pZE32luc plasmid backbone (Lutz and Bujard, Nucleic Acids Research, Vol.25:6, 1997, pp.1203–1210) was genetically engineered by: 1) Replacing PLlacO-1promoter and luciferase gene with a tetracycline inducible promoter (PLtetO-1 promoter) driving expression of S. pyogenes Cas9 (optionally containing an N-terminal 6xHis tag), which was amplified from the plasmid pRC319. Also, BsaI restriction sites in the plasmid backbone were removed to enable Golden Gate Assembly of the phagemid using the BsaI restriction enzyme (See, for example, Citorik et al. Nature Biotechnol.2014.) 2) Incorporating of crRNA leader and CRISPR array (crRNA and tracrRNA) containing 30 nt spacer sequences targeting one or more conserved Shigella virulence factors. The tracrRNA is located upstream of the PLtet0-1promoter and 6xHis-Cas9 construct. The tracrRNA and Cas9 construct were amplified together from plasmid pRC319. 3) Incorporating the 1.4 kb Φ2457T packaging (pac3mut) sequence, and 4) Incorporating the 1.4 kb Φ2457T origin of replication (ORF55 containing four knockout mutations). Attorney Docket No.29539-0809WO1 The RGN phagemids were further genetically engineered to include specific CRISPR spacers. Specifically, the RGN phagemids were genetically engineered by adapting CRISPR spacers to target conserved Shigella virulence genes ipaH4, mxiH, mxiD, and virB (Figs.3A- 3B), which were incorporated into the optimized phagemid backbones (Figs.2A-2D) and packaged into Φ2457T transducing particles to create ΦRGNs. Efficacy was analyzed with broth infection assays and the results are shown in Fig. 3A. At high multiplicities of infection (MOIs), treatment with ΦRGNs containing random spacers lacking target sequences in Shigella reduced the number of virulent cells recovered 46-fold, showing some off-target effects. However, treatment with ΦRGNs targeting single virulence genes (e.g., virB) or two virulence factors (virB and mxiH) reduced the number of virulent cells recovered 4.7 x 103-fold and 6.6 x 103-fold, respectively. It was hypothesized that the reduction in virulent cells recovered resulted from induction of cell death or loss of the pathogenicity plasmid. Thus, Φ2457T were successfully delivered RGNs to S. flexneri cells, with sequence-specific targeting of conserved virulence factors to kill Shigella cells in vitro. Next survival of the Shigella cells following RGN delivery was tested. Briefly, S. flexneri donor cells containing RGN phagemids with either a random spacer sequence or the virB-5 spacer sequence that targets the Shigella virB virulence gene were infected with Φ2457Tam3 helper phages at a multiplicity of infection (MOI; ratio of phages to bacteria) of one for two hrs. Subsequently, each ΦRGN was collected from donor cell lysates and used to infect WT S. flexneri 2457T recipient cells at a MOI of 50 for three hrs. Transduced recipient cells were selected by plating onto TSB + Congo red indicator plates supplemented with antibiotics, and eight representative transduced Shigella cells were further re-streaked onto fresh indicator plates. These indicator plates enable differentiation of virulent Shigella cells (red colonies) and avirulent Shigella cells (white colonies). Representative results of the indicator plate phenotypes for each isolate are shown in Fig.3B, in which scanned images of the plates are provided and colony color are designated below the images. Grey circles represent red, virulent colonies; white circles represent white, avirulent colonies; and mixed circles represent a mixture of virulent and avirulent colonies. All CFUs from the random spacer ΦRGN control infections formed virulent colonies (left), while seven of eight CFUs from the virB-5 ΦRGN infection formed avirulent colonies with one mixed colony (right). Thus, the majority of transduced bacteria surviving RGN delivery were rendered avirulent. Attorney Docket No.29539-0809WO1 Assessing the Φ2457T host range for DNA delivery The delivery of DNA payloads by Φ2457Tam3 helper phages to several Shigella and E. coli strains were tested. The results are shown in Figs.4A-4B. Fig.4A shows results from a study where serial dilutions of wild-type (WT) Φ2457T phages were plated onto lawns of various WT Shigella and Escherichia coli strains, and clearings (plaques) represent phage infection. Fig.4B shows results from a study where S. flexneri donor cells harboring pac3mut-ORF55 phagemids were infected with Φ2457Tam3 helper phages and the resulting phage lysates were used to infect the various WT Shigella and E. coli recipient cells. Transduced bacteria containing each putative phagemid were obtained by antibiotic selection and the concentration of transducing phages was enumerated (Fig.4B). The data shown in Figs.4A-4B indicate that Φ2457T has a broader host range for DNA payload delivery than for phage infection. Overall, Φ2457T helper phages can deliver DNA payloads most efficiently to S. flexneri, and approximately 103-fold reduced efficiency to several E. coli, S. sonnei, and S. dysenteriae strains (Figs.4A-4B). Example 2. Enhancing targeted Shigella lysis by ΦRGNs To enhance targeted Shigella lysis by ΦRGNs and prevent off-target effects, for example, off-target lysis of commensal bacterial species, the RGN phagemids are modified by modifying CRISPR spacers to target chromosomal virulence genes. Example 3. Expanding the Φ2457T host range by adding tail fiber sequences into the RGN phagemid The Φ2457T host range can be expanded to include all four species of Shigella. To expand the host range of Φ2457T, Φ2457T tail fiber genes gp46 and gp52, containing the receptor binding domains responsible for determining the host range, are genetically engineered using allele replacement and random mutagenesis. The affinity of the bacteriophage tail fibers for receptors on the bacterial cell surface is modulated by the genetic engineering. The host range of the resulting genetically engineered (also called chimeric) bacteriophages is assessed in vitro broth infection assays. The safety and efficacy of candidate bacteriophages modified tail fibers and an expanded host range are evaluated for their ability to infect a variety of Shigella clinical isolates. The most efficacious tail fibers are incorporated into enhanced ΦRGNs. Next, transduction efficiency with tail fiber variant chimeric bacteriophage particle libraries was tested. Briefly, Φ2457T wild-type ORF52 tail fiber sequence and random Attorney Docket No.29539-0809WO1 Φ2457T ORF52 tail fiber variants introduced through error-prone PCR were cloned into pac3-ORF55 phagemids under control of the native Φ2457T ORF52 promoter. Wild-type and tail fiber variant library phagemids were transformed into S. flexneri amber suppressor strains. The resulting donor strains were infected with Φ2457Tam3ΔORF52::lacZ helper phages at a multiplicity of infection (MOI; ratio of phages to bacteria) of two for two hours. The resulting phage lysates were used to infect S. flexneri strain 2457T, S. sonnei strain 53G, S. dysenteriae strain 1617, and E. coli K12 strain MG1655 recipient cells. Transduced bacteria containing each putative phagemid were selected by plating the bacterial cells on media supplemented with antibiotics, and the concentration of transducing phages was enumerated. The logarithmic-scale transductant forming units (TFU) / mL of WT tail fiber transducing particles and tail fiber variant libraries on each recipient strain were normalized to the transduction efficiency on S. flexneri 2457T and plotted (n=3, ±SD). The results are shown in Fig.5C. As shown in Fig.5C, transduction from tail fiber variant chimeric bacteriophage particle libraries (dark grey) was more efficient on S. sonnei 53G (9-fold), S. dysenteriae 1617 (3-fold), and E. coli K12 MG1655 (9-fold) recipient hosts compared to bacteriophage transducing particles containing wild-type tail fiber sequences (white). Thus, chimeric bacteriophage transducing particle libraries contain tail fiber variants that confer higher transduction efficiency for various recipient bacterial strains. Example 4. Prophetic Example – testing ΦRGNs in a human intestinal organoid- derived epithelial monolayer (HIODEM) model To determine the efficacy of ΦRGNs against clinical isolates of Shigella, a pre- clinical HIODEM model is used. The HIODEM model propagates intestinal tissue that is obtained from a subject as an organoid. Subsequently, the cells are seeded onto a transwell, grown, and differentiated in culture into a mature, polarized monolayer with antigen- sampling M cells, mucus-producing goblet cells, and enterocytes expressing tight junctions and microvilli that approximate the cellular architecture of the gastrointestinal tract. The HIODEM model can test adherence and invasion of pathogens to HIODEMs, barrier breach of HIODEMs by pathogens, and cytokine secretion of HIODEMS. In addition, HIODEMS facilitate microscopy and genomic and proteomic analyses in response to stimuli, such as pathogens. See, for example, Llanos-Chea et al. JPGN.2019 and Nickerson et al. Microbiol. Spectr.2021. Attorney Docket No.29539-0809WO1 EXEMPLARY SEQUENCES Exemplary sequences are described in Table 3. Table 3. Exemplary Sequences SEQ ID Sequence Construct type Description NO 1 ZA22su F Plasmid Constitutive ex ression of su F amber er F- s. o . g of Attorney Docket No.29539-0809WO1 SEQ ID Sequence Construct type Description NO 5 pZE31RGN-virBspcr5- Phagemid RNA-guided nuclease (RGN) phagemid o . ) id ) id o id 52 S. nt n o id Attorney Docket No.29539-0809WO1 SEQ ID Sequence Construct type Description NO chimeric transducing particles with s. e es d- s T Attorney Docket No.29539-0809WO1 SEQ ID Sequence Construct type Description NO 18 mxiDspcr5 CRISPR spacer S. flexneri virulence plasmid-encoded g g g Attorney Docket No.29539-0809WO1 SEQ ID Sequence Construct type Description NO 44 phi2457T ORF57 DNA Adenine AYP69364.1 e es e

Claims

Attorney Docket No.29539-0809WO1 WHAT IS CLAIMED IS:

1. A chimeric bacteriophage particle comprising: a) a recombinant phagemid comprising, in any order: vii) a nucleotide sequence encoding a CRISPR RNA (crRNA) comprising i) one or more spacer sequence(s) that is complementary to one or more target nucleotide sequence(s) encoding one or more virulence factor(s) in a bacterial species, and wherein the one or more spacer sequences(s) are located between a first inverted repeat sequence and a second inverted repeat sequence; viii) a nucleotide sequence encoding a tracrRNA; ix) a nucleotide sequence encoding a CRISPR-associated (cas) nuclease; x) a nucleotide sequence comprising a bacteriophage packaging (pac) site; xi) a nucleotide sequence comprising a bacteriophage origin of replication; and xii) optionally, a nucleotide sequence encoding a non-native tail fiber or variant thereof, wherein the non-native tail fiber or variant thereof is from a bacteriophage that can infect a bacterial strain and b) one or more tail fibers, wherein the one or more tail fibers is a non-native tail fiber or variant thereof.

2. The chimeric bacteriophage particle of claim 1, wherein the bacterial stain is a strain of Shigella or Escherichia.

3. The chimeric bacteriophage particle of claim 1 or 2, wherein the virulence factor is selected from ipaH4, mxiH, mxiD, virB, iutA, and sitA.

4. The chimeric bacteriophage particle of any one of claims 1-3, wherein the spacer sequence has at least 80-100% (e.g., 90%, 95%, or 100%) sequence identity to SEQ ID NOs.14-31.

5. The chimeric bacteriophage particle of any one of claims 1-4, wherein the cas nuclease is a Cas9 nuclease.Attorney Docket No.29539-0809WO1 6. The chimeric bacteriophage particle of any one of claims 1-5, wherein the cas nuclease is a Streptococcus pyogenes Cas9 nuclease, a Staphylococcus aureus Cas9 nuclease, a homolog thereof, or a variant thereof.

7. The chimeric bacteriophage particle of any one of claims 1-6, wherein the nucleotide sequence encoding the cas nuclease has at least 90%, 95%, or 100% sequence identity to SEQ ID NO:

32.

8. The chimeric bacteriophage particle of any one of claims 1-7, wherein the nucleotide sequence comprising the pac site has at least 90%, 95%, or 100% sequence identity to SEQ ID NO:

34.

9. The chimeric bacteriophage particle of any one of claims 1-8, wherein the nucleotide sequence comprising the bacteriophage origin of replication has at least 90%, 95%, or 100% sequence identity to SEQ ID NO:

35.

10. The chimeric bacteriophage particle of any one of claims 1-9, wherein the nucleotide sequence encoding the non-native tail fiber or variant thereof has: at least 90%, 95%, or 100% sequence identity to SEQ ID NO: 33; at least 90%, 95%, or 99% sequence identity to SEQ ID NO: 38; or at least 90%, 95%, or 99% sequence identity to SEQ ID NO:

39.

11. The chimeric bacteriophage particle of any one of claims 1-10, wherein a plurality of the chimeric bacteriophage particle has a transducing particle titer from about 103to about 1014in a broth infection assay, wherein the broth infection assay comprises a recipient cell selected from S. dysenteriae, S. flexneri, S. boydii, S. sonnei, and Escherichia coli.

12. A chimeric bacteriophage particle library comprising a plurality of unique chimeric bacteriophage particles, wherein each of the unique chimeric bacteriophage particles comprises the chimeric bacteriophage particle of any one of claims 1-11, wherein the nucleotide sequence is a unique nucleotide sequence encoding a unique non-native tail fiber or variant thereof.Attorney Docket No.29539-0809WO1 13. A genetically modified lytic bacteriophage comprising: one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis; and, optionally, a non-native tail fiber from a bacteriophage, or variant thereof.

14. The genetically modified lytic bacteriophage of claim 13, wherein the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis comprises one or more of the following genes from Φ2457T: ORF53, ORF54, ORF55, ORF56, ORF57, ORF64, ORF65, and / or ORF66.

15. The genetically modified lytic bacteriophage of claim 13 or 14, wherein the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis comprises: a mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof; a mutated nucleotide sequence encoding a non-functional DNA helicase or homolog thereof; or a mutated nucleotide sequence encoding a non-functional lysin or homolog thereof.

16. The genetically modified lytic bacteriophage of claim 15, wherein the mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof is a mutated ORF54 gene encoding a non-functional ORF54 gene product.

17. The genetically modified lytic bacteriophage of claim 15 or 16, wherein the non- functional DnaA protein or homolog thereof is a truncated DnaA protein or homolog thereof.

18. The genetically modified lytic bacteriophage of any one of claims 15-17, wherein the mutated nucleotide sequence encoding a non-functional DnaA protein or homolog thereof comprises an amber mutation.Attorney Docket No.29539-0809WO1 19. The genetically modified lytic bacteriophage of any one of claims 15-18, wherein the mutated nucleotide sequence encoding a non-functional DNA helicase or homolog thereof is a mutated ORF55 gene encoding a non-functional ORF55 gene product.

20. The genetically modified lytic bacteriophage of any one of claims 15-19, wherein the non-functional DNA helicase or homolog thereof is a truncated DNA helicase or homolog thereof.

21. The genetically modified lytic bacteriophage of any one of claims 15-20, wherein the mutated nucleotide sequence encoding a non-functional DNA helicase or homolog thereof comprises an amber mutation.

22. The genetically modified lytic bacteriophage of any one of claims 15-21, wherein the mutated nucleotide sequence encoding a non-functional lysin or homolog thereof is a mutated ORF65 gene encoding a non-functional ORF65 gene product.

23. The genetically modified lytic bacteriophage of any one of claims 15-22, wherein the non-functional lysin or homolog thereof is a truncated lysin or homolog thereof.

24. The genetically modified lytic bacteriophage of any one of claims 15-23, wherein the mutated nucleotide sequence encoding a non-functional lysin or homolog thereof comprises an amber mutation.

25. The genetically modified lytic bacteriophage of any one of claims 13-24, wherein the one or more mutated nucleotide sequence(s) encoding a non-functional protein required for bacteriophage DNA replication or host cell lysis comprises deletion or truncation of a nucleotide sequence encoding a tail fiber protein or variant thereof.

26. The genetically modified lytic bacteriophage of any one of claims 13-25, wherein the tail fiber is from a bacteriophage that can infect Shigella.

27. The genetically modified lytic bacteriophage of any one of claims 13-26, wherein the genetically modified lytic bacteriophage cannot replicate in bacterial cells lacking amber suppressor transfer RNAs.Attorney Docket No.29539-0809WO1 28. The genetically modified lytic bacteriophage of any one of claims 13-27, wherein the genetically modified lytic bacteriophage only replicates in bacterial cells comprising amber suppressor transfer RNAs.

29. The genetically modified lytic bacteriophage of claim 27 or claim 28, wherein the bacterial cells are Shigella cells.

30. A genetically modified bacteria cell comprising a vector, wherein the vector comprises one or more nucleotide sequences encoding one or more amber suppressor transfer RNA (tRNA).

31. The genetically modified bacteria cell of claim 30, wherein the one or more nucleotide sequences encoding one or more amber suppressor tRNA encodes a supF amber suppressor tRNA.

32. The genetically modified bacteria cell of claim 30 or claim 31, wherein the one or more nucleotide sequences encoding one or more amber supper tRNAs is operably linked to a constitutive promoter.

33. The genetically modified bacteria cell of any one of claims 30-32, wherein the genetically modified bacteria cell is a genetically modified Shigella cell, optionally a Shigella flexneri cell.

34. The genetically modified bacteria cell of claim 33, further comprising a nucleotide sequence encoding a modified tail fiber of a bacteriophage that can infect a strain of Shigella that is not a Φ2457T bacteriophage.

35. The genetically modified bacteria cell of claim 34, wherein the modified tail fiber is encoded by ORF14 of the Shigella bacteriophage vB_SsoS-ISF002 (SEQ ID NO: 33), or a nucleotide sequence having at least 90%, 95%, or 99% sequence identity thereto.

36. The genetically modified bacteria cell of claim 34, wherein the modified tail fiber or variant thereof is encoded by a nucleotide sequence having at least 90%, 95%, or 99%Attorney Docket No.29539-0809WO1 sequence identity to phi2457T ORF52 (SEQ ID NO: 38) or phi2457T ORF46 (SEQ ID NO: 39).

37. The genetically modified bacteria cell of any one of claims 34-36, wherein the nucleic acid encoding a tail fiber or variant thereof is operably linked to a promoter.

38. The genetically modified bacteria cell of claim 37, wherein the promoter is a Φ2457T ORF52 promoter or a Φ2457T ORF46 promoter.

39. A system for producing the chimeric bacteriophage particle of any one of claims 1-11, wherein the system comprises the genetically modified lytic bacteriophage of any one of claims 13-29 and the genetically modified bacteria cell of any one of claims 30-38.

40. A pharmaceutical composition comprising the chimeric bacteriophage particle of any one of claims 1-11.

41. A method of treating a subject previously identified as having a bacterial infection, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising the chimeric bacteriophage particle of any one of claims 1-11, optionally wherein the bacterial infection is a Shigella infection.

42. The method of claim 41, wherein the subject is a human or a non-human primate.

43. The method of claim 41 or claim 42, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, optionally wherein the pharmaceutically acceptable carrier is a pharmaceutically acceptable excipient.

44. The method of any one of claims 41-43, further comprising administering an effective amount of a second therapeutic agent comprising an anti-diarrheal and / or a rehydration solution.

45. The method of claim 44, wherein the second therapeutic agent is an anti-diarrheal comprising bismuth subsalicylate.Attorney Docket No.29539-0809WO1 46. The method of claim 44, wherein the rehydration solution is selected from an oral rehydration solution and an intravenous rehydration solution.

Images