Recombinant bacterial cell capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide using a tumour-inducible promoter

Abstract

Provided herein are recombinant bacterial cells capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component. The invention also provides promoters, nucleic acids, and cells comprising the same. The invention also provides medical uses for and methods of using the heterologous bacterial cells, promoters, nucleic acids, and cells provided herein.

Description

[0001]Methods and Compositions Field of the invention The present invention is in the field of cancer therapy. Background Immunological cancer therapies including immune checkpoint inhibitors (ICIs), antibody therapies, and engineered cell therapies such as chimeric antigen receptor T-cell (CAR-T) therapies, have changed the treatment landscape of many tumours, proving highly efficacious treatment options for previously intractable cancers. Cancer immunotherapies typically require the infiltration of host and / or therapeutically administered cells into the core of a tumour to be effective. However, the extracellular matrix of the tumour can act as a physical barrier to effective immune cell infiltration into the tumour core, contributing to the development of immune excluded tumors. Immune-excluded tumours are characterised by a tumour microenvironment (TME) which physically excludes immune cells from the tumour core, thereby limiting the efficacy of cancer immunotherapies. The extracellular matrix (ECM) is a major contributor to the exclusive nature of the microenvironment in immune-excluded tumours, which are a sub- set of tumours known as “immunologically cold” tumours. In a significant number of immune-excluded tumours extracellular matrix (ECM) components are present in elevated levels, presenting a barrier to immunotherapies and drastically decreasing their therapeutic impact. The extracellular matrix (ECM) can mediate exclusion in a number of ways; for example, the extracellular matrix (ECM) makes up a dense, highly fibrotic environment with high levels of interstitial pressure which generates biophysical barriers to the infiltration of immune cells and other biologics; and also traps immunosuppressive growth factors and signals directly into immune cells, affecting their behaviour directly and inhibiting their migration and invasion. Among these elevated extracellular matrix (ECM) components are proteoglycans such as hyaluronic acid (HA) and versican. Most solid tumour indications have been shown to have a percentage of immune-excluded patients. For example, it is estimated that about 50% of patients with triple negative breast cancer carry a tumour that is an immune-excluded tumour. Among the indications with the highest percentage of immune exclusion are triple-negative breast cancer; colon cancer; and pancreatic cancer. These are also indications with a highly abundant extracellular matrix deposition, which includes increased levels of proteoglycans (for example, hyaluronic acid (HA)). It is estimated that worldwide immune-excluded tumours can affect more than 3 million new patients every year, and there are currently no adequate therapies for patients with these tumour types, which also do not respond to immunotherapy strategies. Immune- excluded tumours therefore represent a significant challenge to the effective treatment of a large cohort of cancer patients, contributing unnecessary cancer-associated morbidity and mortality. Several avenues have been explored to disrupt the solid tumour stroma in order to remove barriers to infiltration, making immune-excluded tumours accessible to immune cells, and hence more tractable to immunotherapy. For example, some approaches have included using chemotherapeutic agents, radiotherapy, and inflammatory cytokines to potentiate immunotherapy of immune-excluded tumours. However, these approaches do not address the fundamental physical constraints imposed on the tumour by extracellular matrix (ECM); and the untargeted nature of several of these approaches may lead to unwanted side-effects. Previous work has shown that using hyaluronidase to degrade hyaluronic acid (HA) in mouse models of cancer leads to normalised vascular coverage, a reduction in hypoxic levels and increased infiltration, without affecting tumour spread (Jacobetz et al., 2013, “Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer”, Gut, 62(1):112-120; Clift et al., 2019, “Remodeling the Tumor Microenvironment Sensitizes Breast Tumors to Anti-Programmed Death-Ligand 1 Immunotherapy”, Cancer Res., 79(16):4149-4159; each herein incorporated by reference in their entirety). Previous attempts to transfer this to the clinic involved modifying the enzyme through a PEGylation process to increase its time in circulation. This led to toxicity associated with circulating levels of the enzyme, as hyaluronic acid (HA) is produced with high turnover levels in most healthy tissues. In fact, doses administered to patients in clinical trials were up to three orders of magnitude lower than those originally tested in mouse models. Decreasing the dosage of the modified enzyme to reduce toxicity led to reduced efficacy and a Phase III trial was ultimately unsuccessful (Van Cutsem et al., 2020, “Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma”, J Clin Oncol., 38(27):3185- 3194; herein incorporated by reference in its entirety). Subsequent data shows that the doses administered in patients were ineffective in mouse models, demonstrating that the dose reduction caused by toxicity levels likely led to the lack of efficacy found in clinical trials. There therefore exists a need to develop new, safe, and effective therapeutic agents that break down extracellular matrix (ECM) components of immune-excluded tumours, without affecting the stroma of healthy tissues. Brief description of the invention The inventors have developed recombinant cells which are capable of degrading components of the extracellular matrix (ECM) by expressing and optionally secreting extracellular matrix (ECM) degrading polypeptides. The inventors have surprisingly found that the cells are capable of degrading the extracellular matrix (ECM), including the extracellular matrix (ECM) of a tumour. The inventors have also developed pH and hypoxia-inducible promoters, which surprisingly allow the expression of a gene to which the promoter is operably linked within a specific pH range and hypoxic conditions. The pH range and hypoxic conditions in which the pH and hypoxia-inducible promoters are active are the same as the pH and hypoxic conditions that are present in the tumour microenvironment. Accordingly, the inventors have surprisingly developed improved promoters that are capable of being activated in the tumour microenvironment, or to put another way, tumour-inducible promoters. By operably linking the pH and hypoxia-inducible promoters to the extracellular matrix (ECM) degrading polypeptides, the invention allows the expression of the extracellular matrix (ECM) degrading polypeptides and degradation of extracellular matrix (ECM) by said extracellular matrix (ECM) degrading polypeptides may be controlled in response to pH and hypoxia. The inventors have further surprisingly found that when administered to a subject, the recombinant cells home to and accumulate specifically in tumour tissue. In in vitro experiments, the inventors have found that the recombinant cells infiltrate the tumour tissue, and further increase chimeric antigen receptor T-cell (CAR-T cell) killing of tumour cells within the tissue. The inventors have therefore developed recombinant cells that when administered to a subject are capable of specifically localising to and degrading the extracellular matrix (ECM) of a tumour, facilitated improved infiltration of the tumour by therapeutic agents. Accordingly, the inventors have developed recombinant cells that are surprisingly capable of making immune-excluded tumours accessible to therapeutic agents. The inventors have also developed medical methods, medical uses, and therapies relating to the recombinant cells. Detailed description of the invention The invention is as set out in the claims. Recombinant bacterial cells In a first aspect, the invention provides a recombinant bacterial cell capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component. By “capable of expressing” it is meant that the bacterial cell can express a particular polypeptide – for example an extracellular matrix (ECM) degrading polypeptide – under certain conditions, for example by transcribing messenger RNA (mRNA) from a nucleotide sequence encoding said polypeptide, and / or translating said mRNA into said polypeptide. Accordingly, in a related aspect, the invention provides a recombinant bacterial cell that expresses a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component. The heterologous ECM degrading polypeptide may be any ECM degrading polypeptide. In some embodiments the extracellular matrix degrading polypeptide is: a) a hyaluronidase, for example a microbial hyaluronidase or a mammalian hyaluronidase; for example wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; for example wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) neuraminidase, for example a microbial neuraminidase or a mammalian neuraminidase; for example wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) PNGase for example a microbial PNGase or a mammalian PNGase; for example wherein the microbial PNGase is a bacterial PNGase. Various means of making a recombinant bacterial cell capable of expressing a particular polypeptide – for example an extracellular matrix (ECM) degrading polypeptide – are known to the person skilled in the art. For example, a cell may be transformed or transfected with a nucleic acid comprising a nucleotide sequence that encodes the heterologous extracellular matrix degrading (ECM) polypeptide. Accordingly, in one embodiment, the cell comprises a nucleic acid comprising a nucleotide sequence that encodes the heterologous extracellular matrix degrading (ECM) polypeptide. The nucleic acid may be any nucleic acid. Accordingly, in some embodiments, the nucleic acid is DNA. Appropriate forms of DNA are known in the art, and are discussed herein. In some embodiments, the nucleic acid is RNA. Appropriate forms of RNA are known in the art, and include mRNA, single-stranded RNA (ssRNA), double-stranded RNA (dsRNA), self- replicating RNA (srRNA), RNA viral vectors, and the like. As discussed herein, the extracellular matrix (ECM) may comprise proteoglycans. Without wishing to be bound by any theory, it is believed that the degradation of the proteoglycan components of extracellular matrix (ECM) comprised in a tumour will allow improved access of therapeutic agents such as immunotherapy agents into the tumour. As discussed herein, an extracellular matrix (ECM) component that may suitably be targeted for degradation is a proteoglycan. Suitable ECM degrading polypeptides that are capable of degrading proteoglycans are known in the art, and include (but are not limited to): a hyaluronidase, a chondroitin ABC lyase, a neuraminidase, and / or a PNGase. Hyaluronidase, chondroitin ABC lyase, neuraminidase, and PNGase are broadly distributed throughout eukaryotes and prokaryotes. Accordingly, the extracellular matrix (ECM) degrading polypeptide may be selected from: a) a eukaryotic hyaluronidase, a eukaryotic chondroitin ABC lyase, a eukaryotic neuraminidase, and / or a eukaryotic PNGase; and / or b) a prokaryotic hyaluronidase, a prokaryotic chondroitin ABC lyase, a prokaryotic neuraminidase, and / or a prokaryotic PNGase. In some embodiments then, the ECM component is a proteoglycan and the extracellular matrix degrading polypeptide is: a) a hyaluronidase, for example a microbial hyaluronidase or a mammalian hyaluronidase; for example wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; for example wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) neuraminidase, for example a microbial neuraminidase or a mammalian neuraminidase; for example wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) PNGase for example a microbial PNGase or a mammalian PNGase; for example wherein the microbial PNGase is a bacterial PNGase. The prokaryotic extracellular matrix (ECM) degrading polypeptide may be a microbial extracellular matrix (ECM) degrading polypeptide. The microbial extracellular matrix (ECM) degrading polypeptide may suitably be a bacterial extracellular matrix (ECM) degrading polypeptide. The eukaryotic extracellular matrix (ECM) degrading polypeptide may suitably be a mammalian extracellular matrix (ECM) degrading polypeptide, for example a human extracellular matrix (ECM) degrading polypeptide. Accordingly, in some embodiments the extracellular matrix component is a proteoglycan, and: a) the ECM degrading polypeptide is a hyaluronidase optionally a microbial hyaluronidase or a mammalian hyaluronidase; optionally wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) the ECM degrading polypeptide is chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; optionally wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) the ECM degrading polypeptide is neuraminidase, optionally a microbial neuraminidase or a mammalian neuraminidase; optionally wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) the ECM degrading polypeptide is PNGase optionally a microbial PNGase or a mammalian PNGase; optionally wherein the microbial PNGase is a bacterial PNGase. As discussed herein, extracellular matrix (ECM) components that are proteoglycans and which may suitably be targeted for degradation include (but are not limited to) hyaluronic acid (HA) and versican. Hyaluronic acid (HA) is a an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues; and is a major component of the extracellular matrix, contributing to cell proliferation and migration; and the progression of tumors. Hyaluronic acid (HA) has the following structure: Where n is an integer representing the number of monomers in a polymer of hyaluronic acid. As used herein, the terms “hyaluronic acid”, “hyaluronan”, and “HA” are interchangeable. Versican is a large extracellular matrix chondroitin sulfate proteoglycan present in a variety of human tissues, and is encoded by the VCAN gene. Versican is made up of a central protein core bound by multiple chondroitin sulfate chains, and it has 5 different isoforms created by differential or alternative splicing. Versican is involved in cell adhesion, migration, and proliferation; and increased versican expression is associated with tumour growth and metastasis. As is known in the art, hyaluronic acid (HA) may be degraded by a hyaluronidase. Versican may be degraded by different classes of enzymes which target different parts of the glycan chains, including sialic acid, glycosaminoglycans (GAGs), and glycoside bonds. These include a chondroitin ABC lyase, a neuraminidase, and / or PNGase. As used herein, the term “degrading”, “degraded”, or “degrade” relates to the process of breaking down a polymer into its constituent subunits, and may include breaking down a polymer chain of a first length into two polymer chains each of a second, shorter length; and / or the breaking down a polymer chain into its constituent monomers or fragments thereof. Accordingly, in some embodiments: a) the ECM component is hyaluronic acid (HA) and the ECM degrading polypeptide is a hyaluronidase, optionally a microbial hyaluronidase or a mammalian hyaluronidase; optionally wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) the ECM component is Versican and the ECM degrading polypeptide is chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; optionally wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) the ECM component is Versican and the ECM degrading polypeptide is neuraminidase, optionally a microbial neuraminidase or a mammalian neuraminidase; optionally wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) the ECM component is Versican and the ECM degrading polypeptide is PNGase optionally a microbial PNGase or a mammalian PNGase; optionally wherein the microbial PNGase is a bacterial PNGase. As discussed herein, the extracellular matrix (ECM) degrading polypeptide may be any suitable extracellular matrix (ECM) degrading polypeptide, for example any suitable hyaluronidase, chondroitin ABC lyase, neuraminidase, and / or PNGase. In the context of degrading an extracellular matrix (ECM) component in a tumour, it will be understood that an extracellular matrix (ECM) degrading polypeptide (for example, a hyaluronidase, chondroitin ABC lyase, neuraminidase, and / or PNGase) is “suitable” if it is capable of or degrades extracellular matrix (ECM) components in a tumour environment or microenvironment. As is known in the art, a tumour environment or microenvironment may be hypoxic, anaerobic, anoxic, or microaerobic. For example, a tumour environment or microenvironment may have an oxygen concentration of below 2%, for example 0-2% and / or 1-2% (McKeown, 2014, “Defining normoxia, physioxia and hypoxia in tumours – implications for treatment response”, Br. J. Radiol., 87(1035):20130676). A tumour environment or microenvironment may be acidic, for example may have a pH of pH 6.2 ± 0.25 (Chien et al., 2022, “Enhancing the tropism of bacteria via genetically programmed biosensors”, Nat. Biomed. Eng., 6:94-104; the contents of which are herein incorporated by reference in their entirety)). Methods of determining whether an extracellular matrix (ECM) degrading polypeptide is capable of degrading extracellular matrix (ECM) in hypoxic, anaerobic, anoxic, microaerobic, and / or acidic conditions are known in the art, and may be found – for example – in Oueslati et al. 2014, “CTAB turbidimetric method for assaying hyaluronic acid in complex environments and under cross-linked form”, Carbohydrate polymers, 112:102-108 (herein incorporated by reference in its entirety). In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide: a) is a hyaluronidase and comprises or consists of an amino acid sequence of SEQ ID NO: 1; is a chondroitin ABC Lyase and comprises or consists of an amino acid sequence of SEQ ID NO: 3 or 47; is a neuraminidase and comprises or consists of an amino acid sequence of SEQ ID NO: 5; or is a PNGase and comprises or consists of an amino acid sequence of SEQ ID NO: 7; or comprises or consists of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 47; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48. In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide is a bacterial hyaluronidase; optionally wherein the heterologous extracellular matrix (ECM) degrading polypeptide: a) comprises or consists of an amino acid sequence of SEQ ID NO: 1; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2. The term “identical to” is known to the person skilled in the art, and relates to the percentage identity between two or more nucleic acid sequences or two or more amino acid sequences. The terms “identical to” and “sequence identity” are interchangeable – i.e., where a first sequence is X% (where X is an integer between 0 and 100) “identical to” a second sequence, the first sequence shares X% “sequence identity” with the second sequence. To determine the percentage identity of two amino acid sequences or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino acid or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % identity=number of identical overlapping positions / total number of positions×100%). In one embodiment, the two sequences are the same length. Percentage identity between two sequences can also be identified using a mathematical algorithm. One example of a mathematical algorithm for the comparison of two sequences is the algorithm of Karlin and Altschul, 1990, Proc. Natl. Acad. Sci. U.S.A. 87:2264 2268 (herein incorporated by reference in its entirety), modified as in Karlin and Altschul, 1993, Proc. Natl. Acad. Sci. U.S.A. 90:5873 5877 (herein incorporated by reference in its entirety). Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al., 1990, J. Mol. Biol.215:403 (herein incorporated by reference in its entirety). To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., 1997, Nucleic Acids Res. 25:3389 3402 (herein incorporated by reference in its entirety). Alternatively, PSI BLAST can be used to perform an iterated search which detects distant relationships between molecules (Id.). When utilizing BLAST, Gapped BLAST, and PSI Blast programs, the default parameters of the respective programs (e.g., of XBLAST and NBLAST) can be used (see, e.g., National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov). Another example of a mathematical algorithm for the comparison of sequences is the algorithm of Myers and Miller, 1988, CABIOS 4:11 17 (herein incorporated by reference in its entirety). Such an algorithm is incorporated in the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. Another example of a mathematical algorithm for the comparison of two sequences is the algorithm of Thompson et al., 1994, Nucleic Acids Res. 22(22):4673-80 (herein incorporated by reference in its entirety), incorporated into the ClustalW program. The percentage identity between two sequences can be determined using techniques similar to those described above, with or without allowing gaps. In calculating percentage identity, typically only exact matches are counted. In some embodiments, the extracellular matrix (ECM) degrading polypeptide is not: a) a hymenopteran hyaluronidase; optionally a bee venom hyaluronidase, a wasp venom hyaluronidase, or a tiger wasp venom hyaluronidase; b) human hyaluronidase-1 (hHyal-1), human hyaluronidase-2 (hHyal-2), human PH- 20 (hPH-20), or bovine testes hyaluronidase (BTS); c) a Streptomyces koganeiensis hyaluronidase, a Streptomyces zooepidemic hyaluronidase, or a Streptomyces pristinaespiralis hyaluronidase; d) a Streptococcus zooepidemicus hyaluronidase; or e) a Penicillium funiculosum hyaluronidase. In some embodiments, the extracellular matrix (ECM) degrading polypeptide is not: a) an influenza neuraminidase, optionally an avian influenza neuraminidase; b) a Clostridium perfringens neuraminidase, optionally NanI or NanJ from Clostridium perfringens; c) a Chinese hamster ovary (CHO) cell sialidase or a Chinese hamster ovary (CHO) cell neuraminidase; d) a Bacteroides fragilis neuraminidase, optionally NanH from Bacteroides fragilis; or e) a Streptococcus pneumoniae neuraminidase. As will be appreciated, for a gene to be expressed from a nucleic acid, it may be advantageous or required to incorporate a promoter into the nucleic acid. Accordingly, in some embodiments, the nucleic acid further comprises a promoter. The term “promoter” is known to the person skilled in the art, and is typically a portion of a nucleic acid comprising a nucleotide sequence to which proteins (for example, sigma factors, transcription factors, and RNA polymerase) bind in order to initiate or drive transcription of a single nucleic acid (for example, RNA or mRNA) transcript from the nucleic acid (for example, DNA) downstream of the promoter. In some embodiments, the nucleotide sequence encoding the heterologous extracellular matrix (ECM) degrading polypeptide is operably linked to the promoter. By “operably linked”, it is meant that the promoter is capable of initiating or driving transcription of a single nucleic acid transcript (for example, RNA or mRNA) comprising a nucleotide sequence encoding the heterologous extracellular matrix (ECM) degrading polypeptide from the nucleic acid (for example, DNA). A promoter may be a constitutive promoter or may be an inducible promoter. The term “constitutive promoter” and “inducible promoter” are known to the person skilled in the art. In some instances, it may be advantageous to control expression of gene encoding a heterologous extracellular matrix (ECM) degrading polypeptide or transcription of a single nucleic acid transcript (for example, RNA or mRNA) comprising a nucleotide sequence encoding the heterologous extracellular matrix (ECM) polypeptide from the nucleic acid (for example, DNA). As will be appreciated, this may be achieved using an inducible promoter from which gene expression or single nucleic acid transcription is initiated or driven in response to the presence or concentration of a particular molecule, or in response to particular environmental conditions such as pH, oxygen concentration, and / or temperature. Accordingly, in some embodiments, the promoter is an inducible promoter. In particular, it may be advantageous to restrict expression of the heterologous extracellular matrix (ECM) degrading polypeptide by the cell to the tumour environment or tumour microenvironment. Accordingly, in some embodiments, the inducible promoter is a tumour-inducible promoter. As discussed herein, the tumour environment or tumour microenvironment may be anaerobic, anoxic, or microaerobic; and / or may have an exemplary oxygen concentration of below 2%, for example between 0-2% and / or between 1-2% (McKeown, 2014, “Defining normoxia, physioxia and hypoxia in tumours – implications for treatment response”, Br. J. Radiol., 87(1035):20130676). A tumour environment or microenvironment may be acidic, for example may have a pH of pH 6.2 ± 0.25 (Chien et al., 2022, “Enhancing the tropism of bacteria via genetically programmed biosensors”, Nat. Biomed. Eng., 6:94-104; herein incorporated by reference in its entirety)). To restrict expression of the extracellular matrix (ECM) degrading polypeptide by the cell to the tumour environment or tumour microenvironment, therefore, initiation of gene expression or transcription of a single nucleic acid transcript from the nucleic acid by the inducible promoter may suitably occur in hypoxic, anaerobic, anoxic, or microaerobic conditions and / or acidic conditions – in other words, the inducible promoter (such as a tumour-inducible promoter) may suitably be a hypoxia-inducible promoter and / or a pH- inducible promoter. Initiation of gene expression or transcription of a single nucleic acid transcript from the nucleic acid by the inducible promoter may suitably not occur in oxic conditions and / or alkaline conditions – in other words, the inducible promoter (such as a tumour-inducible promoter) may suitably be a hypoxia-inducible promoter. As will be appreciated, a promoter comprises multiple promoter elements, each comprising discrete nucleotide sequences. Promoter elements may be selected from the group comprising or consisting of: an RNA polymerase binding site, a ribosome binding site (RBS), a -35 sequence, a -10 sequence, a Shine-Dalgarno sequence, a Pribnow Box, an operator sequence, a TATA box, a transcription factor binding site, or any combination thereof. Promoter elements may be arranged in a variety of different ways, and the sequences of each promoter element varied, in order to alter the activation specificity (i.e., the conditions in which the promoter initiates or drives transcription of a single nucleic acid transcript from the nucleic acid downstream of the promoter) of a promoter or the strength (i.e., the number of copies of a single nucleic acid transcript transcribed under the control of the promoter in a given period of time) of a promoter. Promoter elements may also be arranged, and the sequences of each promoter element varied, in order to alter the translation initiation specificity or rate. Exemplary promoter elements that may be arranged or varied to alter the translation initiation or rate include, for example, the ribosome binding site (RBS). For example, to design an inducible promoter that is a hypoxia-inducible promoter and / or a pH-inducible promoter may be generated by modifying single nucleotides in the promoter sequence, for example in particular promoter elements, as disclosed in Davis et al., 2011, “Design, construction and characterization of a set of insulated bacterial promoters”, Nucleic Acids Res., 39(3):1131-1141, and Chen et al., 2018, “Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors”, Nat. Commun., 9:64 (each herein incorporated by reference in their entirety). Any promoter element may be modified; and any modification may be made. For example, a modification of a single nucleotide may include modification to introduce a single nucleotide polymorphism, a transition mutation, a transversion mutation, a base insertion, and / or a base deletion of the single nucleotide. In some embodiments, the inducible promoter (such as a tumour-inducible promoter) is a hypoxia-inducible promoter. Any hypoxia-inducible promoter may be incorporated into the nucleic acid; however, in some embodiments, optionally the hypoxia-inducible promoter is selected from the group comprising or consisting of: LOR9, LOR7, LOR1, pflE, pepT, YbiY, and pvhb. In some embodiments, the hypoxia-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) between about 0% and about 2%, about 0.2% and about 1.8%, about 0.4% and about 1.6%, about 0.6% and about 1.4%, about 0.8% and about 1.2%, about 0% and about 1%, about 0.2% and about 0.8%, about 0.4 and about 0.6%, 1% and 2%, about 1.2% and about 1.8%, about 1.4% and about 1.6%; b) between 0% and 2%, 0.2% and 1.8%, 0.4% and 1.6%, 0.6% and 1.4%, 0.8% and 1.2%, 0% and 1%, 0.2% and 0.8%, 0.4 and 0.6%, 1% and 2%, 1.2% and 1.8%, 1.4% and 1.6%; c) below about 2%, below about 1.5%, below about 1.6%, below about 1.4%, below about 1.2%, below about 1%, below about 0.8%, below about 0.6%, below about 0.4%, below about 0.2% or lower; d) below 2%, below 1.5%, below 1.6%, below 1.4%, below 1.2%, below 1%, below 0.8%, below 0.6%, below 0.4%, below 0.2% or lower; e) about 2%, about 1.8%, about 1.6%, about 1.4%, about 1.2%, about 1%, about 0.8%, about 0.6%, about 0.4%, about 0.2%; and / or f) 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.4%, 0.2%. In some embodiments, the hypoxia-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide in normoxia; optionally wherein the hypoxia-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) above about 6%, above about 5%, above about 4%, or above about 3%; b) above 6%, above 5%, above 4%, or above 3%; c) about 6%, about 5%, about 4%, about 3%; and / or d) 6%, 5%, 4%, 3%. Hypoxic conditions may be simulated in vitro by culturing a cell in liquid culture media, where the surface of the air-liquid interface is completely covered or substantially covered with a layer of mineral oil. In some embodiments, the hypoxia-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide when the recombinant cell is incubated in culture media under mineral oil. Appropriate methods for culturing a cell in such conditions may be determined by the person skilled in the art; however, in some embodiments the cell is optionally incubated at 37°C for 18 hours. In some embodiments the hypoxia-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; In some embodiments, the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. In some embodiments, the inducible promoter (such as a tumour-inducible promoter) is a pH-inducible promoter. Any pH-inducible promoter may be incorporated into the nucleic acid; however, in some embodiments, optionally the pH inducible promoter is selected from the group comprising or consisting of: LPR7, LPR1, LPR9, Stm1787, hyaA, P170-IL, P170-MG, P1, P2, and P3. In some embodiments, the pH-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.5 and about pH 7, about pH 5.6 and about pH 6.9, about pH 5.7 and about pH 6.8, about pH 5.8 and about pH 6.7, about pH 5.9 and about pH 6.6, about pH 6.0 and about pH 6.5, about pH 6.1 and about pH 6.4, about pH 6.2 and about pH 6.3; b) between pH 5.5 and pH 7, pH 5.6 and pH 6.9, pH 5.7 and pH 6.8, pH 5.8 and pH 6.7, pH 5.9 and pH 6.6, pH 6.0 and pH 6.5, pH 6.1 and pH 6.4, pH 6.2 and pH 6.3; c) below about pH 7, below about pH 6.9, below about pH 6.8, below about pH 6.7, below about pH 6.6, below about pH 6.5, below about pH 6.4, below about pH 6.3, below about pH 6.2, below about pH 6.1, below about pH 6.0, below about pH 5.9, below about pH 5.8, below about pH 5.7, below about pH 5.6, or lower; d) below pH 7, below pH 6.9, below pH 6.8, below pH 6.7, below pH 6.6, below pH 6.5, below pH 6.4, below pH 6.3, below pH 6.2, below pH 6.1, below pH 6.0, below pH 5.9, below pH 5.8, below pH 5.7, below pH 5.6; e) about pH 5.5, about pH 5.6, about pH 5.7, about pH 5.8, about pH 5.9, about pH 6.0, about pH 6.1, about pH 6.2, about pH 6.3, about pH6.4, about pH 6.5, about pH 6.6, about pH 6.7, about pH 6.8, about pH 6.9, or about pH 7; and / or f) pH 5.5, pH 5.6, pH 5.7, pH 5.8, pH 5.9, pH 6.0, pH 6.1, pH 6.2, pH 6.3, pH6.4, pH 6.5, pH 6.6, pH 6.7, pH 6.8, pH 6.9, or pH 7. In some embodiments, the pH-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.9 and about pH 6.5, about pH 5.95 and about pH 6.45, about pH 6.0 and about pH 6.4, about pH 6.05 and about pH 6.35, about pH 6.1 and about 6.3, or about pH 6.15 and about pH 6.25; b) between pH 5.9 and pH 6.5, pH 5.95 and pH 6.45, pH 6.0 and pH 6.4, pH 6.05 and pH 6.35, pH 6.1 and 6.3, or pH 6.15 and pH 6.25; c) about pH 5.9, about pH 5.95, about pH 6.0, about pH 6.05, about pH 6.1, about pH 6.15, about pH 6.2, about pH 6.25, about pH 6.3, about pH 6.35, about pH 6.4, about pH 6.45, or about pH 6.5; and / or d) pH 5.9, pH 5.95, pH 6.0, pH 6.05, pH 6.1, pH 6.15, pH 6.2, pH 6.25, pH 6.3, pH 6.35, pH 6.4, pH 6.45, or pH 6.5. In some embodiments, the pH-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105. In some embodiments, the pH-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, or SEQ ID NO: 61; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, or SEQ ID NO: 60, or SEQ ID NO: 61. In some embodiments, the pH-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an alkaline pH. The term “alkaline pH” is known to the person skilled in the art. A solution has an “alkaline pH” if it has a pH of between pH 7 and pH 14. An inducible promoter (such as a tumour-inducible promoter) as disclosed herein may be a pH-inducible and / or hypoxia-inducible promoter. Accordingly, in one embodiment, the inducible promoter (such as a tumour-inducible promoter) is a pH-inducible and / or hypoxia-inducible promoter. In some embodiments, the pH-inducible and hypoxia- inducible promoter is LOR9. In some embodiments: a) the LOR9 promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 73, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 73; and / or b) the LOR9 promoter is encoded by a nucleotide sequence of SEQ ID NO: 55 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55. The pH-inducible promoter and hypoxia-inducible promoter may be activated at the same pH and O2 concentration as the pH-inducible promoters and hypoxia-inducible promoters provided herein. As disclosed herein, the promoter elements may be arranged in a variety of different ways, and the sequences of each promoter element varied. Accordingly, in some embodiments, the hypoxia-inducible promoter comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding site, a modified ribosome binding site (RBS), a modified -35 sequence, a modified -10 sequence, a modified Shine-Dalgarno sequence, a modified Pribnow Box, modified operator sequence, a modified TATA box, a modified transcription factor binding site; or any combination thereof. In some embodiments, the pH-inducible promoter comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding site, a modified ribosome binding site (RBS), a modified -35 sequence, a modified -10 sequence, a modified Shine-Dalgarno sequence, a modified Pribnow Box, modified operator sequence, a modified TATA box, a modified transcription factor binding site, or any combination thereof. A promoter may be identified as a pH-inducible promoter and / or a hypoxia-inducible promoter using methods known in the art. Exemplary methods of identifying a promoter as pH-inducible are disclosed in Chen et al., 2018, “Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors”, Nat. Commun., 9:64 (herein incorporated by reference in its entirety). For example, a cell may be provided comprising a nucleic acid comprising a nucleotide sequence encoding a promoter sequence operably linked to a nucleotide sequence encoding a detectable marker, for example a detectable marker that is capable of producing light. Suitable detectable markers may include, for example, fluorescent proteins (including but not limited to: GFP, YFP, RFP, mCherry, BFP, iLOV and any variant or derivative thereof), luciferase, horseradish peroxidase, alkaline phosphatase, and the like. The cell may be cultured in suitable test conditions, for example in culture media that has a test pH and / or in culture media that is hypoxic and / or has a hypoxic O2 concentration as discussed herein. Suitable controls may be employed, for example culturing the cell in suitable control conditions. In the case of identifying pH-inducible and / or hypoxia-inducible promoters, the control condition may culturing the cell in culture media that has a pH that is different from the test pH and / or in media that is normoxic or not hypoxic and / or has a normoxic O2 concentration as discussed herein. The presence or absence of a signal (for example, light of a given wavelength) by the cell may then be detected in the test conditions and / or the control conditions. Where the signal is detected in the test conditions, the promoter is determined to be induced in said test conditions – for example, the promoter may be determined to be a pH-inducible promoter and / or a hypoxia-inducible promoter. Similarly, where suitable controls are employed, where the signal is detected in the test conditions but is not detected in the control conditions or is detected at a statistically significantly lower level in the control conditions than in the test conditions, the promoter is determined to be induced in said test conditions – for example, the promoter may be determined to be a pH-inducible promoter and / or a hypoxia-inducible promoter. The signal may be present at a level that is 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 20x, 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, 1000x, 2000x, 3000x, 4000x, 5000x, 6000x, 7000x, 8000x, 9000x, 10000x, or more times higher in the test conditions than in the control conditions. Suitable methods of detecting a detectable marker are known in the art, and include, for example, visual inspection, light microscopy, fluorescence microscopy, flow cytometry such as fluorescence activated cell sorting (FACS), and microplate readers. It will be understood that a promoter may be dual-inducible promoter that is hypoxia- and pH-inducible. For example, a dual inducible promoter may be induced in hypoxic conditions and may have increased activity at a given pH, for example at a pH that is an acidic pH as provided herein. Accordingly, in some embodiments, the dual inducible promoter is a hypoxia-inducible promoter the activity of which is increased in acidic conditions. In some embodiments, the dual inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) between about 0% and about 2%, about 0.2% and about 1.8%, about 0.4% and about 1.6%, about 0.6% and about 1.4%, about 0.8% and about 1.2%, about 0% and about 1%, about 0.2% and about 0.8%, about 0.4 and about 0.6%, 1% and 2%, about 1.2% and about 1.8%, about 1.4% and about 1.6%; b) between 0% and 2%, 0.2% and 1.8%, 0.4% and 1.6%, 0.6% and 1.4%, 0.8% and 1.2%, 0% and 1%, 0.2% and 0.8%, 0.4 and 0.6%, 1% and 2%, 1.2% and 1.8%, 1.4% and 1.6%; c) below about 2%, below about 1.5%, below about 1.6%, below about 1.4%, below about 1.2%, below about 1%, below about 0.8%, below about 0.6%, below about 0.4%, below about 0.2% or lower; d) below 2%, below 1.5%, below 1.6%, below 1.4%, below 1.2%, below 1%, below 0.8%, below 0.6%, below 0.4%, below 0.2% or lower; e) about 2%, about 1.8%, about 1.6%, about 1.4%, about 1.2%, about 1%, about 0.8%, about 0.6%, about 0.4%, about 0.2%; and / or f) 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.4%, 0.2%. In some embodiments, the dual-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide in normoxia; optionally wherein the dual-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) above about 6%, above about 5%, above about 4%, or above about 3%; b) above 6%, above 5%, above 4%, or above 3%; c) about 6%, about 5%, about 4%, about 3%; and / or d) 6%, 5%, 4%, 3%. In some embodiments, the dual-inducible promoter is activated and drives expression and / or increased expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.5 and about pH 7, about pH 5.6 and about pH 6.9, about pH 5.7 and about pH 6.8, about pH 5.8 and about pH 6.7, about pH 5.9 and about pH 6.6, about pH 6.0 and about pH 6.5, about pH 6.1 and about pH 6.4, about pH 6.2 and about pH 6.3; b) between pH 5.5 and pH 7, pH 5.6 and pH 6.9, pH 5.7 and pH 6.8, pH 5.8 and pH 6.7, pH 5.9 and pH 6.6, pH 6.0 and pH 6.5, pH 6.1 and pH 6.4, pH 6.2 and pH 6.3 c) below about pH 7, below about pH 6.9, below about pH 6.8, below about pH 6.7, below about pH 6.6, below about pH 6.5, below about pH 6.4, below about pH 6.3, below about pH 6.2, below about pH 6.1, below about pH 6.0, below about pH 5.9, below about pH 5.8, below about pH 5.7, below about pH 5.6, or lower; d) below pH 7, below pH 6.9, below pH 6.8, below pH 6.7, below pH 6.6, below pH 6.5, below pH 6.4, below pH 6.3, below pH 6.2, below pH 6.1, below pH 6.0, below pH 5.9, below pH 5.8, below pH 5.7, below pH 5.6; e) about pH 5.5, about pH 5.6, about pH 5.7, about pH 5.8, about pH 5.9, about pH 6.0, about pH 6.1, about pH 6.2, about pH 6.3, about pH6.4, about pH 6.5, about pH 6.6, about pH 6.7, about pH 6.8, about pH 6.9, or about pH 7; and / or f) pH 5.5, pH 5.6, pH 5.7, pH 5.8, pH 5.9, pH 6.0, pH 6.1, pH 6.2, pH 6.3, pH6.4, pH 6.5, pH 6.6, pH 6.7, pH 6.8, pH 6.9, or pH 7. In some embodiments, the dual-inducible promoter is activated and drives expression and / or increased expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.9 and about pH 6.5, about pH 5.95 and about pH 6.45, about pH 6.0 and about pH 6.4, about pH 6.05 and about pH 6.35, about pH 6.1 and about 6.3, or about pH 6.15 and about pH 6.25; b) between pH 5.9 and pH 6.5, pH 5.95 and pH 6.45, pH 6.0 and pH 6.4, pH 6.05 and pH 6.35, pH 6.1 and 6.3, or pH 6.15 and pH 6.25; c) about pH 5.9, about pH 5.95, about pH 6.0, about pH 6.05, about pH 6.1, about pH 6.15, about pH 6.2, about pH 6.25, about pH 6.3, about pH 6.35, about pH 6.4, about pH 6.45, or about pH 6.5; and / or d) pH 5.9, pH 5.95, pH 6.0, pH 6.05, pH 6.1, pH 6.15, pH 6.2, pH 6.25, pH 6.3, pH 6.35, pH 6.4, pH 6.45, or pH 6.5. In some embodiments, the dual-inducible promoter is LOR9 or LOR1. In some embodiments, the dual-inducible promoter is encoded by a nucleotide sequence of SEQ ID SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55, or SEQ ID NO: 56. Dual-inducible promoters may be identified using the same methods as set out for identifying pH-inducible and hypoxia-inducible promoters. If a promoter is identified as a pH-inducible promoter and a hypoxia-inducible promoter, it may be identified as a dual- inducible promoter. If a promoter is identified as a hypoxia-inducible promoter, and the activity of the hypoxia-inducible promoter increases in conditions that are the same as the conditions that identify a promoter as a pH-inducible promoter, the promoter may be determined to be a dual-inducible promoter. In some embodiment, the promoter may be a hybrid promoter. Transcription from a hybrid promoter may be activated by two or more transcription factors, either separately or concurrently. Hybrid promoters may be constructed, for example, by encoding operator sites for multiple transcription factors in a single promoter; operably linking a gene to two consecutive promoters, each comprising specific regulatory features and transcription start sites; or by engineering different transcription factors that bind to the same operator. Optimal activity of the heterologous extracellular matrix (ECM) degrading polypeptide may depend on the localisation of the heterologous extracellular matrix (ECM) degrading polypeptide with respect to the recombinant cell. For example, expression of or localisation of the extracellular matrix (ECM) degrading polypeptide in the cell or display of the extracellular matrix (ECM) degrading polypeptide on the surface of the cell may restrict degradation of extracellular matrix (ECM) to the vicinity of the cell, providing controlled degradation of extracellular matrix (ECM) by the cell. Secretion of the extracellular matrix (ECM) degrading polypeptide from the cell may allow the extracellular matrix (ECM) degrading polypeptide to degrade extracellular matrix (ECM) that is not proximal to or contacted by the cell. Without wishing to be bound by theory, it is thought that extracellular matrix (ECM) degrading polypeptide secreted from the cell may diffuse through extracellular matrix (ECM) or a tumour, allowing it to degrade extracellular matrix (ECM) in portions of the tumour that are not immediately contacted by the cell. It is expected that the polypeptide may not diffuse outside of the tumour (for example, due to the size and / or short half-life of the polypeptide), may not retain extracellular matrix (ECM) degrading activity outside of the tumour, and / or may not diffuse outside of the tumour in an amount, quantity, or concentration to effectively degrade the extracellular matrix (ECM) present in tissues outside of the tumour. In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide: a) is secreted from the cell; b) is displayed on the surface of the cell; or c) is expressed in the cell. In a preferred embodiment, the heterologous extracellular matrix (ECM) degrading polypeptide is secreted from the cell. By “secreted by the cell” it is meant actively exported by the cell across the plasma membrane or plasma membranes of the cell, from the cytosol to the extracellular milieu, via a polypeptide secretion system that is expressed by the cell. The polypeptide secretion system may be endogenous to the cell or may be introduced to the cell. Suitable polypeptide secretion systems may be selected from the group comprising or consisting of: a type 1 secretion system (T1SS), a type 2 secretion system (T2SS), a type 3 secretion system (T3SS), a flagellar type 3 secretion system (F-T3SS), a non-flagellar type 3 secretion system (NF-T3SS), a type 4 secretion system (T4SS), a type 5 secretion system, a type 5 secretion system, a type 6 secretion system (T6SS), a type 7 secretion system (T7SS), a type 8 secretion system (T8SS), a type 9 secretion system (T9SS), a type 10 secretion system (T10SS), a type 11 secretion system (T11SS), an autotransporter, a Usp45-mediated secretion mechanism, a Sec dependent secretion system, an ompin- dependent secretion system, a Tat dependent secretion system, a Lactococcus secretion system, or any combination thereof. Suitable secretion systems and cognate signal sequences capable of directing a polypeptide for secretion by these secretion systems are disclosed in WO 2021 / 255480 A1, Burdette et al., 2018, “Developing Gram-negative bacteria for the secretion of heterologous proteins” Microb. Cell Factories, 17:196, Costa et al., 2015, “Secretion systems in Gram-negative bacteria: structural and mechanistic insights”, Nat. Rev. Microbiol., 13:343-359, Zhang et al., 2006, “Extracellular accumulation of recombinant proteins fused to the carrier protein YebF in Escherichia coli”, Nat. Biotechnol., 24:100-104, Borrero et al., 2011, “Use of the usp45 lactococcal secretion signal sequence to drive the secretion and functional expression of enterococcal bacteriocins in Lactococcus lactis”, Appl. Microbiol. Biotechnol., 89(1):131-143, and Kim et al., 2014, “Simple amino acid tags improve both expression and secretion of Candida antarctica lipase B in recombinant Escherichia coli”, Biotechnol. Bioeng., 112(2):346-355, each of which is herein incorporated by reference in its entirety. As is known in the art, secretion of a polypeptide from a bacterial cell via a particular secretion system requires the polypeptide to comprise a secretion signal or secretion domain that targets the polypeptide to said particular secretion system. However, such secretion signals or secretion domains have degenerate sequences; and accordingly, a secretion signal or secretion domain that is not 100% identical to the consensus sequence or a known sequence of said secretion signal or secretion domain may still be secreted by the target secretion system. For example, a secretion signal or secretion domain may be at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the consensus sequence or known sequence of a secretion signal or domain and be secreted by the target secretion system. Suitable secretion signals or secretion domains may be identified by methods known in the art. Such methods may include, for example, culturing in test conditions a bacterial cell expressing a fusion polypeptide comprising the secretion signal or secretion domain and a second polypeptide of interest in liquid culture media; separating the bacterial cell from the liquid culture media; and identifying the presence or absence of the fusion polypeptide or second polypeptide of interest in the separated culture media. Suitable controls may be employed, for example separately culturing a bacterial cell expressing a control polypeptide comprising the second polypeptide but that does not comprise the secretion signal or secretion domain; separating the bacterial cell from the liquid culture media; and identifying the presence or absence of the control polypeptide in the separated culture media. A further suitable control may be used where the fusion polypeptide is placed under the control of an inducible promoter. Such a control may include separately culturing a bacterial cell expressing a control polypeptide comprising the secretion signal or secretion domain and second polypeptide; separating the bacterial cell from the liquid culture media; and identifying the presence or absence of the control polypeptide in the separated culture media. Where the fusion polypeptide or second polypeptide of interest is present in the separated culture media of the test conditions, the fusion polypeptide or second polypeptide of interest is determined to be secreted by the bacterial cell. Similarly, where suitable controls are employed, where the fusion polypeptide or second polypeptide of interest is present in the separated culture media of the test conditions, but the control polypeptide is absent from the control conditions or is present at a statistically significantly lower level in the control conditions than in the test conditions, the fusion polypeptide or second polypeptide of interest is determined to be secreted by the bacterial cell. The fusion polypeptide or second polypeptide of interest may be present in the test condition at a level that is 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 20x, 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, 200x, 300x, 400x, 500x, 600x, 700x, 800x, 900x, 1000x, 2000x, 3000x, 4000x, 5000x, 6000x, 7000x, 8000x, 9000x, 10000x, or more times higher than the control polypeptide is present in the control conditions. Methods of detecting protein in separated liquid culture media are known to the person skilled in the art, and include, for example, western blot analysis, HPLC analysis, ELISA analysis, and the like. Methods of separating bacterial cells from liquid culture media or liquid media are known to the person skilled in the art, and include – for example – centrifugation and filtration. For example, in some embodiments, bacterial cells may be separated from liquid culture media or liquid media by centrifugation at 4000 rpm, 5000 rpm, 6000 rpm, 7000 rpm, 8000 rpm, 9000 rpm, 10,000 rpm, 11,000 rpm, 12,000 rpm, 13,000 rpm or more for a specified period. In some embodiments, bacterial cells may be separated from liquid culture media or liquid media by centrifugation for 1 minute, 2 minutes, 3 minutes, 4 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, or more. In some embodiments, bacterial cells may be separated from liquid culture media or liquid media by filtration. As the skilled person will be aware, bacterial cells from different bacterial species have different sizes. For example, an Escherichia coli cell has a diameter of approximately 0.25 to 1 µm and a length of 1-2 µm; whereas a Lactococcus lactis cell has a length of approximately 0.5-1.5 µm and a diameter of approximately 0.7-1 µm. Appropriate filter sizes for separating bacterial cells from liquid culture media or liquid media may be determined by the person skilled in the art. Exemplary secretion domains and the exemplary secretion system via which a polypeptide comprising said secretion domain may be exported from the cell are set out in Table 1. Table 1 Secretion system Secretion domain Sec-dependent secretion system N-terminal PelB sequence Sec-dependent secretion system N-terminal YebF carrier protein Autotransporter N-terminal CtxB signal sequence C-terminal AIDA-I autotransporter Flagellar T3SS N-terminal FliC signal sequence Lactococcus secretion system N-terminal Usp45 signal sequence Such secretion domains may be used to target a fusion polypeptide for secretion by the cell. Accordingly, in some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide is a fusion polypeptide comprising: a) an ECM degrading domain; and b) a secretion domain. In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide comprises two secretion domains. In some embodiments, the secretion domain is selected from the group comprising or consisting of: a PelB secretion signal sequence, a YebF carrier protein, a CtxB signal sequence, an AIDA-I autotransporter, a FliC signal sequence, and a Usp45 signal sequence, or any combination thereof. As will be appreciated, where secretion of the polypeptide requires the presence of a particular cognate secretion system (for example, the FliC signal sequence and the T3SS), a cell should be selected comprising said secretion system. As described herein, however, the polypeptide secretion system may be endogenous to the cell or may be introduced to the cell, using methods known in the art. In some embodiments, the secretion domain: a) comprises or consists of an amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36. In some embodiments, the fusion polypeptide: a) comprises an ECM degrading domain that comprises a hyaluronidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 2, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46; or b) comprises an ECM degrading domain that comprises a neuraminidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114, or an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, or SEQ ID NO: 114; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, or SEQ ID NO: 115. In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide comprises a cleavage domain. By the term “cleavage domain” it is meant a portion of a polypeptide that is capable of being cleaved or split by a polypeptide-degrading polypeptide, such as a protease or a peptidase (for example, an endopeptidase or exopeptidase). Cleavage of the cleavage domain may be site- or sequence-specific, for example the cleavage domain may comprise an amino acid sequence that is or is capable of being recognised and cleaved or split by a specific protease or peptidase that is capable of cleaving or splitting said amino acid sequence. Such an amino acid sequence may be referred to as a “protease site” or a “peptidase site”. In some embodiments, the cleavage domain is positioned between the extracellular matrix (ECM) degrading domain and the secretion domain, thereby allowing cleavage of the extracellular matrix (ECM) degrading domain from the secretion domain. It is thought that cleavage of the ECM degrading domain from the secretion domain at the cleavage domain may improve secretion of the extracellular matrix (ECM) degrading polypeptide from the cell. Without wishing to be bound by theory, some secretion domains as provided herein are known to associate with the outer membrane or outer membrane proteins of a cell during the secretion of cargo proteins fused to said secretion domains; and it is thought that the cleavage of a cargo protein (for example, an extracellular matrix (ECM) degrading domain as provided herein) from the secretion domain may increase release of the extracellular matrix (ECM) degrading polypeptide from the surface of the cell into the extracellular milieu. In some embodiments, the cleavage domain comprises an amino acid sequence that is or is capable of being recognised and cleaved or split by a protease or peptidase that is present in a target tissue or tumour as described herein, for example a protease or peptidase that is produced naturally by a human subject. Human proteases and peptidases are known in the art, and may be selected from the groups comprising: a metalloprotease (including a matrix metalloprotease (MMP)), a serine protease, a cysteine protease, a threonine protease, an aspartic protease, a glutamic protease, an asparagine protease, and a peptide lyase. In some embodiments, the cleavage domain comprises an amino acid sequence that is or is capable of being recognised and cleaved or split by a matrix metalloprotease (MMP), i.e., the cleavage domain comprises a matrix metalloprotease (MMP) site. It may be advantageous to provide a nucleotide sequence encoding a transcriptional regulatory polypeptide, which is capable of modulating transcription from the promoter in response to the presence of a given molecule or certain conditions. Accordingly, in one embodiment, the nucleic acid further comprises nucleotide sequence encoding a transcriptional regulatory polypeptide. The transcriptional regulatory polypeptide may suitably be a transcriptional repressor, a transcriptional activator, an operator protein, or any combination thereof. The transcriptional regulatory polypeptide may be functionally related to the secretion signal or secretion domain. Accordingly, in some embodiments, the secretion domain is a FliC signal sequence, the transcriptional regulatory peptide is selected from the group comprising or consisting of: a FliC repressor; optionally wherein the FliC repressor is a GadE repressor. It is thought that GadE represses fliC transcription by binding directly to the fliC promoter to repress transcription. GadE expression should interrupt the flagellin protein to be secreted by the T3SS and to compete with the heterologous extracellular matrix (ECM) degrading polypeptide secretion In some embodiments, the transcriptional regulatory peptide: a) comprises or consists of an amino acid sequence of SEQ ID NO: 49; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 49; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 50, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 50. The recombinant bacterial cell may be any suitable bacterial cell. However, the cell is advantageously a bacterial cell that is genetically tractable; actively migrates to tumours; and has an intrinsic ability to trigger an immune response within a tumour. Because of the infection risks and side-effects (for example, systemic inflammation, toxic shock syndrome, and the like) associated with administering a pathogenic cell to a subject, it is considered advantageous if the cell is not a pathogenic cell or is a non-pathogenic cell. By “pathogenic cell” it is meant a cell that is capable of causing a disease in a subject, for example by presenting virulence factors such as persistence in immune cells. In some embodiments, therefore, the cell is a non-pathogenic bacterial cell, a commensal cell, or a probiotic cell. As is known in the art, a commensal cell is a cell that is a constituent of the healthy microbiome of a subject, for example on the surface of a subject’s body or mucous membranes, and which does not usually cause disease or infection in a healthy subject. Accordingly, a commensal cell may be a constituent of the gut microbiome, the skin microbiome, the conjunctival microbiome, the urethral and bladder microbiome, the vaginal microbiome, the uterine microbiome, the oral microbiome, the nasal microbiome, the lung microbiome, and / or the biliary tract microbiome. A probiotic cell is a cell that promotes the formation or maintenance of a healthy microbiome in a subject, and does not usually cause disease or infection in a healthy subject. A probiotic cell may be a cell that is a constituent of the healthy microbiome of a subject. As disclosed herein, the tumour environment or microenvironment may be hypoxic, anaerobic, anoxic, or microaerobic. The recombinant cell according to the present invention is therefore advantageously capable of surviving and / or replicating in a hypoxic, anaerobic, anoxic, or microaerobic environment. Thus, in some embodiments, the cell is a facultatively anaerobic cell. The recombinant bacterial cell may be any suitable bacterial cell. In some embodiments, the cell is: a) a gram-negative bacterial cell; or b) a gram-positive bacterial cell. In some embodiments, the gram-negative bacterial cell is selected from the group comprising or consisting of: an Escherichia coli cell; Optionally wherein the gram-negative bacterial cell is an Escherichia coli K12 cell or an Escherichia coli Nissile cell; optionally wherein the gram-negative bacterial cell is an Escherichia coli K12 cell; optionally wherein the Escherichia coli K12 cell is selected from the group comprising or consisting of: an Escherichia coli K12 MG1655 cell, an Escherichia coli K12 58 cell, an Escherichia coli K12 679 cell, an Escherichia coli K12 WG1 cell, an Escherichia coli K125K cell, an Escherichia coli K1258-161 cell, an Escherichia coli K12 AB284 cell, an Escherichia coli K12 AB311 cell, an Escherichia coli K12 AG1 cell, an Escherichia coli K12 C600 cell, an Escherichia coli K12 Cavalli Hfr cell, an Escherichia coli K12 DH1 cell, an Escherichia coli K12 DH5-α cell, an Escherichia coli K12 DP50 cell, an Escherichia coli K12 EMG2 cell, an Escherichia coli K12 EPI100- T1R cell, an Escherichia coli K12 H1443 cell, an Escherichia coli K12 HB101 cell, an Escherichia coli K12 Hfr3000 cell, an Escherichia coli K12 Hfr 3000 X74 cell, an Escherichia coli K12 HMS 174 cell, an Escherichia coli K12 JM109 cell, an Escherichia coli K12 TG1 cell, an Escherichia coli K12 TOP10 cell, an Escherichia coli K12 W1485 cell, an Escherichia coli K12 W208 cell, an Escherichia coli K12 W3110 cell, an Escherichia coli K12 W945 cell, an Escherichia coli K12 WA704 cell, and an Escherichia coli K12 WG1 cell. In some embodiments, the Escherichia coli K12 cell is an Escherichia coli K12 MG1655 cell. E. coli K12 (such as E. coli K12 MG1655) is a non-pathogenic facultatively anaerobic rod- shaped gram negative bacterium that has a good safety profile, is capable of localising to a tumour, and is genetically tractable. Considered as safe by regulators, E. coli K12 (such as E. coli K12 MG1655) has the ability to home to the tumour after intravenous administration with a high maximum tolerated dose of 5x107CFU (Kang et al., 2020, “Imaging of tumor colonization by Escherichia coli using 18F-FDS PET”, Theranostics, 2020;10(11):4958-4966; herein incorporated by reference in its entirety). In some embodiments, the gram-positive bacterial cell is a lactic acid bacterial cell; optionally wherein the lactic acid bacterial cell is selected from the group comprising or consisting of: a Lactococcus lactis cell, a Lactobacillus cell, and a Bifidobacterium cell; optionally wherein the gram-positive bacterial cell is a Lactococcus lactis MG1363 cell. Lactococcus lactis MG1363, is a plasmid-free lactic acid bacteria regarded as safe by regulators. As a single-membrane gram-positive cocci, the molecular biology tools to express heterologous proteins are well defined allowing the use of the strain as a live vector to express therapeutics (Jacouton et al., 2019, “Anti-tumoral Effects of Recombinant Lactococcus lactis Strain Secreting IL-17A Cytokine”, Front Microbiol., 9:3355; herein incorporated by reference in its entirety). As discussed herein, the cell is advantageously not a pathogenic cell or is a non-pathogenic cell. Pathogenic cells may be attenuated by methods known in the art; however, the safety profile of these cells may not be comparable to that of non-pathogenic cells. Accordingly, in some embodiments, the cell is not an attenuated bacterial cell. By “attenuated bacterial cell” it is meant a bacterial cell with reduced virulence compared to a pathogenic bacterial cell of the same strain or species that has not been “attenuated”. By “attenuated” it is meant procedures that weaken an agent of disease (a pathogen). An attenuated pathogen is weakened, less vigorous compared to one that is non-attenuated. Attenuation may be due to genetic mutations. Genetic mutations may be engineered or result from passaging of the pathogen in cell culture. In some embodiments, the cell is not: a) a Salmonella cell; optionally a Salmonella bongori cell, a Salmonella cholreaesuis cell, a Salmonella enterica cell, a Salmonella enteritidis cell, a Salmonella paratyphi cell, a Salmonella typhi cell, or a Salmonella typhimurium cell; b) a Vibrio cell; optionally a Vibrio cholerae cell or a Vibrio fischeri cell; c) a Shigella cell; optionally a Shigella boydii cell, a Shigella dysenteriae cell, a Shigella flexneri cell, or a Shigella sonnei cell; d) a Lactobacillus cell; optionally a Lactobacillus bulgaricus cell or a Lactobacillus plantarum cell; e) a Listeria cell; optionally a Listeria monocytogenes cell; f) an Enterococcus cell; optionally an Enterococcus faecium cell; g) a Streptococcus cell; optionally a Streptococcus pyogenes cell, a Streptococcus zooepidemic cell, or a Streptococcus pneumoniae cell; h) a pathogenic Escherichia coli cell; optionally an Enteroinvasive Escherichia coli (EIEC) cell, an Adherent-Invasive Escherichia coli (AIEC) cell, an Enteroaggregative Escherichia coli (EAEC) cell, a Shiga Toxin-producing Escherichia coli (STEC) cell, an Enterotoxigenic Escherichia coli (ETEC) cell, or an Enterohemorrhagic Escherichia coli (EHEC) cell; i) a Bacillus cell, optionally a Bacillus CGMCC No. 5744 cell or a Bacillus subtilis; j) an Arthrobacter cell, optionally an Arthrobacter sphaeroides cell; k) a Streptomyces cell, iptionally a Streptomyces koganeiensis cell, a Streptomyces pristinaespiralis cell, or a Streptomyces zooepidemic cell; or l) a Bacteroides cell, optionally a Bacteroides uniformis cell. The cell provided herein is a bacterial cell. Accordingly, as will be understood, the cell is not a eukaryotic cell such as a fungal cell, a mammalian cell, or a plant cell. For example, the cell is not a Pichia cell such as a Pichia pastoris cell (also known as a Komagataella pastoris cell). In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide does not localise to an intracellular compartment of the cell. In some embodiments, the heterologous extracellular matrix (ECM) degrading polypeptide does not localise to a membrane or cell wall of the cell. It may be desirable to include transcriptional regulatory elements in the nucleic acid. Accordingly, in some embodiments, the nucleic acid further comprises a nucleotide sequence encoding a transcriptional regulatory element. In some embodiments, the nucleotide sequence encoding the heterologous extracellular matrix degrading (ECM) polypeptide is operably linked to the transcriptional regulatory element. In some embodiments, the transcriptional regulatory element is selected from the group comprising or consisting of: a terminator sequence, a repressor binding sequence, an insulator, an operator sequence, or any combination thereof. In some embodiments: a) the terminator is selected from the group comprising or consisting of: rrnB T1 / T2; optionally wherein the terminator sequence has a sequence of SEQ ID NO: 51; b) the repressor binding sequence is selected from the group comprising or consisting of: FNR; optionally wherein the repressor binding sequence has a sequence of SEQ ID NO: 52; and / or c) the insulator sequence is selected from the group comprising or consisting of: RiboJ; optionally wherein the insulator sequence has a sequence of SEQ ID NO: 53. Suitable nucleic acids are known in the art. In some embodiments, the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC). In some embodiments, optionally the nucleic acid is a plasmid. In some embodiments, the nucleic acid integrated into the genome of the cell. In some embodiments, the nucleic acid may comprise a detectable marker, for example an antibiotic resistance marker or a colorimetric detectable marker such as LacZ, or a detectable marker that is capable of producing light. Suitable detectable markers may include, for example, fluorescent proteins (including but not limited to: GFP, YFP, RFP, mCherry, BFP, and any variant or derivative thereof), luciferase, horseradish peroxidase, iLOV, and the like. In preferred embodiments, the nucleic acid does not comprise an antibiotic resistance marker. Accordingly, in preferred embodiments, the recombinant bacterial cell provided herein is not resistant to an antibiotic. Methods of introducing a nucleic acid into a cell are known in the art, and include but are not limited to: electroporation, heat-shock transformation, conjugation, or any combination thereof. Methods of integrating a nucleic acid into the genome of a cell are known in the art, and include but are not limited to: homologous recombination, non- homologous end joining (NHEJ), transposition, retrotransposition, and chromosomal editing methods such as CRISPR-Cas editing, zinc-finger nuclease (ZNF) editing, TALEN editing, and any combination thereof. Such methods are described, for example, in Sambrook, Molecular Cloning: A Laboratory Manual, 4thEd. Cold Spring Harbor, N.Y.:Cold Spring Harbor Laboratory Press, 2012. As discussed above, bacteria – including those provided herein – are known to accumulate in a tumour. Accordingly, in some embodiments, the cell is capable of accumulating in a target tissue or tumour. By “accumulating in a target tissue or tumour” or “accumulates in a target tissue or tumour” it is meant that the cell is present at a higher level or concentration in a target tissue or tumour compared to the area surrounding the target tissue or tumour. A cell may be determined as having “accumulated in a target tissue or tumour” if, for example, a higher number of colony forming units (CFU) of the cell are recoverable or are recovered from a given volume or mass of the target tissue or tumour than are recoverable or are recovered from an equivalent volume or mass of the area surrounding the target tissue or tumour. CFU may be determined by methods known in the art, and include plate counting methods and microscopic determination methods. Such methods may be performed in vitro or in vivo. Where the methods are performed in vivo, the cell may be administered to a subject. The cell may be determined as having “accumulated in a target tissue or tumour” if, for example, a higher number of colony forming units (CFU) of the cell are recoverable or are recovered from a given volume or mass of the target tissue or tumour in a subject than are recoverable or are recovered from an equivalent volume or mass of a tissue or tumour that is not the target tissue or tumour in the same subject. Methods of recovering tissue or tumour samples for CFU determination are known in the art. Similarly, a cell provided herein may comprise a detectable marker, for example a detectable marker that is capable of producing light. Suitable detectable markers may include, for example, fluorescent proteins (including but not limited to: GFP, YFP, RFP, mCherry, BFP, and any variant or derivative thereof), luciferase, horseradish peroxidase, and the like. Such a cell may be administered to a subject. The cell may be determined as having “accumulated in a target tissue or tumour” if, for example, a higher level of a signal produced by the detectable marker (for example, light of a given wavelength) is detectable or detected in the target tissue or tumour in a subject than is detectable or detected in a tissue or tumour that is not the target tissue or tumour in the same subject. Methods of detecting the accumulation of luminescent and / or fluorescent cells in a subject are known in the art, and include, for example, the IVIS Spectrum In Vivo Imaging System as described for example in Warawa and Lawrenz, 2013, “Bioluminescent Imaging of Bacteria During Mouse Infection”, In: Badr, C. (eds) Bioluminescent Imaging. Methods in Molecular Biology, vol 1098. Humana Press, Totowa, NJ (herein incorporated by reference in its entirety). As will be understood, the term “target tissue” as used herein relates to a tissue that contains a tumour or a cancer. Promoters, nucleic acids, and cells of the invention In a second aspect, the invention provides a hypoxia-inducible promoter, wherein the hypoxia-inducible promoter is a promoter as provided herein. In some embodiments, the hypoxia-inducible promoter is optionally wherein the hypoxia-inducible promoter is an engineered hypoxia-inducible promoter. In some embodiments: a) the hypoxia-inducible promoter is an LOR9, an LOR7 promoter, or an LOR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. In preferred embodiments, the hypoxia-inducible promoter is an LOR9 promoter, for example a promoter encoded by a nucleotide sequence of SE ID NO: 55; or a sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55. In preferred embodiments, the hypoxia-inducible promoter is an LOR1 promoter, for example a promoter encoded by a nucleotide sequence of SE ID NO: 55; or a sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55. In a further aspect, the invention provides a pH-inducible promoter, wherein the pH- inducible promoter is a promoter as described herein. In some embodiments, the pH- inducible promoter is optionally an engineered pH-inducible promoter. In some embodiments: a) the pH-inducible promoter is an LPR9, an LPR7 promoter, or an LPR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO: 59; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO: 59. By “engineered hypoxia-inducible promoter” and “engineered pH inducible promoter” (each also referred to herein as an “engineered promoter”) it is meant that the nucleotide sequence of the promoter is not a natural promoter sequence. An engineered promoter may be derived from a natural promoter, however, and may be generated by modification of any promoter element or transcriptional regulatory element described herein, for example promoter elements selected from the group comprising or consisting of: a ribosome binding site (RBS), an operator binding site, and an RNA polymerase binding site. For example, a natural promoter may be modified by replacing a promoter element or transcriptional regulatory element that is endogenous to the natural promoter with a heterologous promoter element or transcriptional regulatory element. An engineered promoter may be generated by mutagenesis of a natural promoter or another engineered promoter, for example by error-prone PCR, site-directed mutagenesis, chemical mutagenesis, or any combination thereof. Methods of determining whether a promoter is a hypoxia-inducible promoter and / or a pH-inducible promoter are provided herein, and may be applied to determine whether a promoter is an engineered hypoxia-inducible promoter and / or an engineered pH-inducible promoter. In a further aspect, provided herein is a tumour-inducible promoter. In some embodiments, the tumour-inducible promoter is a hypoxia-inducible promoter provided herein. In some embodiments, the tumour-inducible promoter is a pH-inducible promoter provided herein. In some embodiments, the tumour-inducible promoter is a hypoxia- inducible and pH-inducible promoter provided herein. In a further aspect, the invention provides a nucleic acid comprising a nucleotide sequence of the hypoxia-inducible promoter as provided herein and / or the pH-inducible promoter as provided herein. In a further aspect, the invention provides a nucleic acid comprising a nucleotide sequence of the tumour-inducible promoter provided herein. In a further aspect, the invention provides a nucleic acid comprising a nucleotide sequence encoding an extracellular matrix (ECM) degrading polypeptide. In some embodiments, the extracellular matrix (ECM) degrading polypeptide encoded by the nucleotide sequence is the heterologous extracellular matrix (ECM) degrading polypeptide provided herein. In some embodiments, the nucleic acid further comprises a promoter; optionally wherein the promoter is the promoter as provided herein. In some embodiments, the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the promoter. In some embodiments, the nucleic acid further comprises a transcriptional regulatory element; optionally wherein the transcriptional regulatory element is the transcriptional regulatory element as provided herein. In some embodiments, the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the transcriptional regulatory element. In some embodiments, the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC); optionally wherein the nucleic acid is a plasmid. In a further aspect, the invention provides a cell comprising the engineered hypoxia- inducible promoter provided herein, the engineered pH-inducible promoter provided herein, and / or the nucleic acid provided herein. In some embodiments, the nucleic acid is: a) extrachromosomal; or b) integrated into the genome of the cell. In some embodiments, the cell is a recombinant bacterial cell; optionally wherein the cell is a recombinant bacterial cell provided herein. Medical methods and medical uses of the recombinant bacterial cell provided herein As discussed herein, the recombinant bacterial cell of the invention may be useful in medicine, particularly in treating cancer. Accordingly, in one aspect the invention provides the recombinant bacterial cell provided herein for use in medicine. In a related aspect, the invention provides the recombinant bacterial cell provided herein for use as a medicament. In a further aspect, the invention provides the recombinant bacterial cell provided herein for use in treating cancer. In a further related aspect, the invention provides use of the recombinant bacterial cell provided herein in the manufacture of a medicament for the treatment of cancer. In one aspect, the invention provides a method of treating cancer with the recombinant bacterial cell provided herein. In one aspect, the invention provides the cell provided herein for use in medicine. In a related aspect, the invention provides the cell provided herein for use as a medicament. In a further aspect, the invention provides the cell provided herein for use in treating cancer. In a further related aspect, the invention provides use of the cell provided herein in the manufacture of a medicament for the treatment of cancer. In one aspect, the invention provides a method of treating cancer using the cell provided herein. In some embodiments, the medical and / or therapeutic uses and methods provided herein comprise administering an effective dose of the recombinant bacterial cell or cell to a subject. The subject may be any suitable subject, however in some preferred embodiments the subject is human. Suitably, the subject may have cancer, may have been diagnosed with cancer, may be suspected to have cancer, or may be recovering from cancer. In some embodiments, the cancer is a tumour solid cancer. In preferred embodiments, the cancer is an immune-excluded solid tumour cancer and / or an immune-excluded tumour. As used herein, the terms “immune-excluded solid tumour cancer” and “immune- excluded tumour” are interchangeable. As discussed herein, immune-excluded tumours are characterised by a tumour microenvironment (TME) which physically and biochemically excludes immune cells from the tumour core, thereby limiting the efficacy of cancer immunotherapies. Other characteristics of immune-excluded tumours include but are not limited to: high levels of stromal deposition which prevents effective infiltration of different subpopulations of immune cells into the tumour microenvironment; collapsed vasculature; low levels of oxygen; and an acidic pH. Cancers and tumours that may suitably be treated with the recombinant bacterial cell or cell provided herein are disclosed in Wilkinson et al. (2017) Oxford Handbook of Clinical Medicine (10th Ed), Oxford University Press, and Cassidy et al. (2015) Oxford Handbook of Oncology (4thEd), Oxford University Press (each herein incorporated by reference in their entirety). In some embodiments, the cancer comprises extracellular matrix. In some embodiments, the cancer is a cancer selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer. The cancer may be a primary cancer or a secondary cancer, for example a metastatic cancer. In some embodiments, the cancer is not a cancer that does not comprise extracellular matrix. In some embodiments, the cancer is not a blood cancer. In some embodiments, the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, lymphoma. In one aspect, the invention provides a composition comprising the recombinant bacterial cell provided herein or the cell provided herein. In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent, excipient, adjuvant, buffer, salt, or the like. Suitable pharmaceutical compositions are known in the art. Exemplary pharmaceutical compositions may be found, for example, in Tovey, 2018, Pharmaceutical Formulation: The Science and Technology of Dosage Forms: Volume 64 (Drug Discovery), Royal Society of Chemistry, and Niazi, 2019, Handbook of Pharmaceutical Manufacturing Formulations (3rdEd.), CRC Press (each herein incorporated by reference in their entirety). In a related aspect, the invention provides the composition provided herein for use in medicine. In a further related aspect, the invention provides the composition provided herein for use as a medicament. In a further related aspect, the invention provides the composition provided herein for use in a method of treating cancer. In a further related aspect, the invention provides use of the composition provided herein in manufacturing a medicament for the treatment of cancer. In one aspect, the invention provides a method of treating cancer using the composition provided herein. In some embodiments, the medical and / or therapeutic uses and methods provided herein comprise administering an effective dose of the composition to a subject. In some embodiments, the subject has cancer. In some embodiments, the cancer is a tumour solid cancer. In preferred embodiments, the cancer is an immune-excluded solid tumour cancer and / or an immune-excluded tumour. As used herein, the terms “immune-excluded solid tumour cancer” and “immune- excluded tumour” are interchangeable. As discussed herein, immune-excluded (or “immunologically cold”) tumours are characterised by a tumour microenvironment (TME) which physically excludes immune cells from the tumour core, thereby limiting the efficacy of cancer immunotherapies. Other characteristics of immune-excluded (or “immunologically cold”) tumours include but are not limited to: high levels of stromal deposition which prevents effective infiltration of different subpopulations of immune cells into the tumour microenvironment; collapsed vasculature; low levels of oxygen; and an acidic pH. Cancers and tumours that may suitably be treated with the recombinant bacterial cell or cell provided herein are disclosed in Wilkinson et al. (2017) Oxford Handbook of Clinical Medicine (10th Ed), Oxford University Press, and Cassidy et al. (2015) Oxford Handbook of Oncology (4thEd), Oxford University Press (each herein incorporated by reference in their entirety). In some embodiments, the cancer is a cancer selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer. The cancer may be a primary cancer or a secondary cancer, for example a metastatic cancer. In one aspect, the invention provides a method for degrading extracellular matrix (ECM) in a tissue, comprising contacting the tissue with the recombinant bacterial cell provided herein, the cell provided herein, or the composition provided herein. The method may be an in vitro method or an in vivo method. In some embodiments, the method is an in vitro method. In some embodiments the method is an in vivo method, for example an in vivo medical method. In some embodiments, the method comprises administering the recombinant bacterial cell, the cell, or the composition to a subject. The subject may be any subject discussed herein. In some embodiments, the subject has a disease. In preferred embodiments, the disease is cancer. The cancer may be any cancer as discussed herein; however, in some embodiments, the cancer comprises extracellular matrix. In some embodiments the cancer is a solid tumour cancer, optionally wherein the cancer is an immune-excluded solid cancer. In some embodiments, the cancer is a cancer selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer. The cancer may be a primary cancer or a secondary cancer, for example a metastatic cancer. In some embodiments, the cancer is not a cancer that does not comprise extracellular matrix. In some embodiments, the cancer is not a blood cancer. In some embodiments, the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, lymphoma. As disclosed herein, the subject may be any suitable subject; however, in some embodiments, the subject is a human subject. In one aspect, the invention provides use of the recombinant bacterial cell provided herein, the cell provided herein, or the composition provided herein to degrade extracellular matrix (ECM). In some embodiments, the use is an in vitro use or an in vivo use. In some embodiments, the use comprises administering the recombinant bacterial cell, the cell, or the composition to a subject. The subject may be any subject provided herein. In embodiments comprising the administration of the recombinant bacterial cell, cell, or composition provided herein, in some embodiments the recombinant bacterial cell, the cell, or the composition is administered to a subject by a route selected from the group comprising or consisting of: oral administration, intraocular administration, intravenous administration, intraarterial administration, intraperitoneal administration, intramuscular administration, intratumoural administration, buccal administration, nasal administration, pulmonary administration. In some embodiments, the recombinant bacterial cell, the cell, or the composition is administered by injection, for example by intravenous injection, intratumoural injection, intraperitoneal injection, intraocular injection, intraarterial injection, or intramuscular injection. In some embodiments, the recombinant bacterial cell, the cell, or the composition is administered as a tablet, a capsule, a powder, a bolus, a suspension, or a solution, for example by oral administration. In some embodiments, the recombinant bacterial cell, the cell, or the composition is administered as a spray, for example by nasal administration and / or by pulmonary administration. In some embodiments, following administration the recombinant bacterial cell or cell accumulates in a target tissue or tumour in the subject. The term “accumulating in a target tissue or tumour” or “accumulates in a target tissue or tumour” is discussed herein. In some embodiments, the recombinant bacterial cell or cell degrades the extracellular matrix (ECM) of the target tissue or tumour. For example, the recombinant bacterial cell or cell may degrade any extracellular matrix (ECM) component disclosed herein, for example by expressing an extracellular matrix (ECM) degrading polypeptide as provided herein. The extracellular matrix (ECM) degrading polypeptide may be any extracellular matrix (ECM) degrading polypeptide provided herein; however, in a preferred embodiment the extracellular matrix (ECM) degrading polypeptide is secreted by the cell. Without wishing to be bound by theory, such degradation of extracellular matrix (ECM) in a target tissue or tumour will allow the entry of immune cells and / or cancer therapeutics such as immunotherapy agents into the tissue or tumour. Without wishing to be bound by theory, it is thought that entry of immune cells into immune excluded tumours will enable the efficacy of immunotherapeutic strategies which activate said immune cells to eliminate cancer cells. Entry of a cancer therapeutic into the tissue or tumour will allow the cancer therapeutic to have the relevant therapeutic effect on the tissue or tumour, or will improve the therapeutic effect of the cancer therapeutic on the tissue or tumour. In other words, when co-administered, the recombinant bacterial cell provided herein or cell provided herein and cancer therapeutic have a synergistic therapeutic effect on the target tissue, tumour, and / or cancer. As will be appreciated, it may be advantageous to administer the recombinant bacterial cell provided herein, the cell provided herein, or composition provided herein to a subject at the same time or at approximately the same time as the subject is administered a therapeutic agent. The therapeutic agent may be any suitable therapeutic agent; however, the therapeutic agent is preferably a cancer therapeutic. Accordingly, in one embodiment, the recombinant bacterial cell provided herein, the cell provided herein, or composition provided herein is: a) administered prior to subsequent administration of a cancer therapeutic; and / or b) co-administered with a cancer therapeutic. The cancer therapeutic may be any suitable cancer therapeutic; however, in preferred embodiments the cancer therapeutic is a cancer immunotherapy. In some embodiments, the cancer therapeutic is selected from the group comprising or consisting of: an antibody (optionally selected from the group comprising or consisting of: an immune checkpoint inhibitor (ICI), T-cell engager, and a bispecific antibody or an antibody-drug conjugate), a hormonal therapy, a targeted therapy, an immunotherapy, a cell therapy (optionally selected from the group comprising or consisting of: a T-cell, a CAR-T cell, and a T4 cell), a chemotherapy agent (optionally selected from the group comprising or consisting of: FOLFOX, Gemcitabine, Paclitaxel, Cisplatin, Epirubicin and Irinotecan) an Immunomodulator (optionally selected from the group comprising or consisting of: a cytokine and a chemokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), and a second live biotherapeutic (optionally selected from the group comprising or consisting of: an engineered live biotherapeutic and a recombinant bacterial cell). In some embodiments, the immune checkpoint inhibitor is selected from the group comprising or consisting of: an anti-PD-1 antibody and an anti-CTLA-4 antibody, an anti- LAG3 antibody, an anti-PDL1 antibody, and anti-TIGIT antibody, an anti-TIM3 antibody, an anti-NKG2A antibody, an anti-BTLA antibody, and anti-GITR antibody, an anti-ICOS antibody, an anti-VISTA antibody. In some embodiments the cell therapy is selected from the group comprising or consisting of: A tumour infiltrating lymphocyte (TIL), a T cell with an engineered T cell receptor (TCR), a CAR T cell, a Natural Killer cell. In some embodiments the chemotherapy is selected from the group comprising or consisting of an alkylating agent (optionally temozolomide and carboplatin), an anti-metabolite (optionally 5-FU or gemcitabine), an anti-tumour antibiotic (optionally doxorubicin), a topoisomerase inhibitor (optionally irinotecan), a mitotic inhibitor (optionally a taxane, optionally paclitaxel or docetaxel), a corticosteroid (optionally dexamethasone). In one aspect, the invention provides a pharmaceutical composition comprising the recombinant bacterial cell provided herein or the cell provided herein, and a cancer therapeutic, for use in treating cancer. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent, excipient, adjuvant, buffer, salt, or the like. Suitable pharmaceutical compositions are known in the art. Exemplary pharmaceutical compositions may be found, for example, in Tovey, 2018, Pharmaceutical Formulation: The Science and Technology of Dosage Forms: Volume 64 (Drug Discovery), Royal Society of Chemistry, and Niazi, 2019, Handbook of Pharmaceutical Manufacturing Formulations (3rdEd.), CRC Press (each herein incorporated by reference in their entirety). In one aspect, the invention provides a combination comprising the recombinant bacterial cell provide herein or cell provided herein and a cancer therapeutic for use in treating cancer. In one aspect, the invention provides a combination comprising a cancer therapeutic and the recombinant bacterial cell provided herein or cell provided herein for use in treating cancer. In one embodiment, the combination may be provided as a composition, optionally wherein the composition is a pharmaceutical composition as described herein. In one embodiment: a) the cancer is a cancer that comprises extracellular matrix; optionally wherein the cancer is selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer; and / or b) the cancer is not a cancer that does not comprise extracellular matrix; optionally wherein the cancer is not a blood cancer; optionally wherein the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, and lymphoma. In one embodiment, the cancer therapeutic is a cancer immunotherapy agent, optionally wherein the cancer immunotherapy agent is selected from the group comprising or consisting of: an antibody (optionally selected from the group comprising or consisting of: an immune checkpoint inhibitor (ICI), T-cell engager, and a bispecific antibody or an antibody-drug conjugate), a cell therapy (optionally selected from the group comprising or consisting of: a T-cell, a CAR-T cell, and a T4 cell), a chemotherapy agent (optionally selected from the group comprising or consisting of: FOLFOX, Gemcitabine, Paclitaxel, Cisplatin, Epirubicin and Irinotecan) an Immunomodulator (optionally selected from the group comprising or consisting of: a cytokine and a chemokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), and a second live biotherapeutic (optionally selected from the group comprising or consisting of: an engineered live biotherapeutic and a recombinant bacterial cell). In some embodiments, the immune checkpoint inhibitor is selected from the group comprising or consisting of: an anti-PD-1 antibody and an anti-CTLA-4 antibody, an anti-LAG3 antibody, an anti-PDL1 antibody, and anti-TIGIT antibody, an anti-TIM3 antibody, an anti-NKG2A antibody, an anti-BTLA antibody, and anti-GITR antibody, an anti-ICOS antibody, an anti-VISTA antibody. In some embodiments the cell therapy is selected from the group comprising or consisting of: A tumour infiltrating lymphocyte (TIL), a T cell with an engineered T cell receptor (TCR), a CAR T cell, a Natural Killer cell. In some embodiments the chemotherapy is selected from the group comprising or consisting of an alkylating agent (optionally temozolomide and carboplatin), an anti-metabolite (optionally 5-FU or gemcitabine), an anti-tumour antibiotic (optionally doxorubicin), a topoisomerase inhibitor (optionally irinotecan), a mitotic inhibitor (optionally a taxane, optionally paclitaxel or docetaxel), a corticosteroid (optionally dexamethasone). In one embodiment, the composition or combination for use is administered to a subject. In one embodiment: a) the recombinant bacterial cell or cell is administered prior to or subsequent to administration of the cancer therapeutic; and / or b) the recombinant bacterial cell or cell is co-administered with the cancer therapeutic. In one embodiment, the composition or combination for use is administered to a subject by a route selected from the group comprising or consisting of: oral administration, intraocular administration, intravenous administration, intraarterial administration, intraperitoneal administration, intramuscular administration, intratumoural administration, buccal administration, nasal administration, pulmonary administration. Suitable methods of administration via these routes are provided herein. In one embodiment, following administration the recombinant bacterial cell or cell accumulates in a target tissue or tumour in the subject. The term “accumulating in a target tissue or tumour” or “accumulates in a target tissue or tumour” is discussed herein. In one embodiment, the recombinant bacterial cell or cell degrades the extracellular matrix (ECM) of the target tissue or tumour. For example, the recombinant bacterial cell or cell may degrade any extracellular matrix (ECM) component disclosed herein, for example by expressing an extracellular matrix (ECM) degrading polypeptide as provided herein. The extracellular matrix (ECM) degrading polypeptide may be any extracellular matrix (ECM) degrading polypeptide provided herein; however, in a preferred embodiment the extracellular matrix (ECM) degrading polypeptide is secreted by the cell. Without wishing to be bound by theory, such degradation of extracellular matrix (ECM) in a target tissue or tumour will allow the entry of immune cells and / or cancer therapeutics such as immunotherapy agents into the tissue or tumour. Accordingly, in on embodiment, degradation of the extracellular matrix (ECM) of the target tissue or tumour allows the host’s immune cells or an administered cancer therapeutic to contact and / or enter the tumour. In one embodiment, said contacting and / or entering the tumour is required for or improves the therapeutic effect of the cancer therapeutic. In other words, when co-administered, the recombinant bacterial cell provided herein or cell provided herein and cancer therapeutic have a synergistic therapeutic effect on the target tissue, tumour, and / or cancer. As will be understood, recombinant bacterial cells and cells provided herein, when administered to a subject, do not persist in and / or do not colonise the subject prior to, during, or following localisation to a target tissue or tumour and / or degradation of extracellular matrix (ECM) in a target tissue or tumour. For example, the recombinant bacterial cells may lyse, be cleared by the immune system during and / or following localisation to a target tissue or tumour and / or degradation of extracellular matrix (ECM) in a target tissue or tumour, or will otherwise be exhausted during and / or following localisation to a target tissue or tumour and / or degradation of extracellular matrix (ECM) in the target tissue or tumour. In this way, the recombinant bacterial cell or cell is exhausted or “used up” during the course of its therapeutic and / or medical use, when administered alone or in combination with a cancer therapeutic, including when administered as part of a composition. As set out herein, in preferred embodiments the nucleic acids provided herein do not comprise an antibiotic resistance marker. Accordingly, in preferred embodiments the recombinant bacterial cell provided herein is not resistant to an antibiotic. A recombinant bacterial cell or cell provided herein may also be cleared from a subject by antibiotic treatment. Suitable antibiotic treatments are known to the person skilled in the art. In one aspect, the invention provides a kit of parts, comprising: a) the recombinant bacterial cell provided herein; b) the engineered hypoxia-inducible promoter provided herein; c) the engineered pH-inducible promoter provided herein; d) the nucleic acid provided herein; e) the cell provided herein; f) the composition provided herein; g) a therapeutic agent, optionally an anti-cancer therapeutic. In one aspect, the invention provides a recombinant bacterial cell, a cell, a pH-inducible promoter, a hypoxia-inducible promoter, a nucleic acid, a use, a composition, a method, and a kit as described substantially herein. The invention also provides the following numbered paragraphs embodiments: 1. A recombinant bacterial cell capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component. 2. The recombinant bacterial cell of paragraph 1, wherein the cell comprises a nucleic acid comprising a nucleotide sequence that encodes the heterologous extracellular matrix degrading (ECM) polypeptide. 3. The recombinant bacterial cell of paragraph 1 or 2, wherein the extracellular matrix degrading polypeptide is: a) a hyaluronidase optionally a microbial hyaluronidase or a mammalian hyaluronidase; optionally wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; optionally wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) neuraminidase, optionally a microbial neuraminidase or a mammalian neuraminidase; optionally wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) PNGase optionally a microbial PNGase or a mammalian PNGase; optionally wherein the microbial PNGase is a bacterial PNGase; optionally wherein the extracellular matrix component is a proteoglycan. 4. The recombinant bacterial cell of any of paragraphs 1-3, wherein: a) the ECM component is hyaluronic acid (HA) and the ECM degrading polypeptide is a hyaluronidase, optionally a microbial hyaluronidase or a mammalian hyaluronidase; optionally wherein the microbial hyaluronidase is a bacterial hyaluronidase; b) the ECM component is Versican and the ECM degrading polypeptide is chondroitin ABC lyase optionally a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; optionally wherein the microbial chondroitin ABC lyase is a bacterial chondroitin ABC lyase; c) the ECM component is Versican and the ECM degrading polypeptide is neuraminidase, optionally a microbial neuraminidase or a mammalian neuraminidase; optionally wherein the microbial neuraminidase is a bacterial neuraminidase; and / or d) the ECM component is Versican and the ECM degrading polypeptide is PNGase optionally a microbial PNGase or a mammalian PNGase; optionally wherein the microbial PNGase is a bacterial PNGase. 5. The recombinant bacterial cell of any of paragraphs 1-3, wherein the heterologous extracellular matrix (ECM) degrading polypeptide: a) is a hyaluronidase and comprises or consists of an amino acid sequence of SEQ ID NO: 1; is a chondroitin ABC Lyase and comprises or consists of an amino acid sequence of SEQ ID NO: 3 or 47; is a neuraminidase and comprises or consists of an amino acid sequence of SEQ ID NO: 5; or is a PNGase and comprises or consists of an amino acid sequence of SEQ ID NO: 7; or comprises or consists of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 47; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48. 6. The recombinant bacterial cell of any of paragraphs 1-4, wherein the heterologous extracellular matrix (ECM) degrading polypeptide is a bacterial hyaluronidase; optionally wherein the heterologous extracellular matrix (ECM) degrading polypeptide: a) comprises or consists of an amino acid sequence of SEQ ID NO: 1; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2. 7. The recombinant bacterial cell of paragraphs 2-6, wherein the nucleic acid further comprises a promoter. 8. The recombinant bacterial cell of paragraph 7, wherein the nucleotide sequence encoding the heterologous extracellular matrix degrading (ECM) polypeptide is operably linked to the promoter. 9. The recombinant bacterial cell of paragraph 7 or 8, wherein the promoter is an inducible promoter. 10. The recombinant bacterial cell of paragraph 9, wherein the inducible promoter is a hypoxia-inducible promoter; optionally wherein the hypoxia-inducible promoter is selected from the group comprising or consisting of: LOR9, LOR7, LOR1, pflE, pepT, YbiY, and pvhb. 11. The recombinant bacterial cell of paragraph 10, wherein the hypoxia-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) between about 0% and about 2%, about 0.2% and about 1.8%, about 0.4% and about 1.6%, about 0.6% and about 1.4%, about 0.8% and about 1.2%, about 0% and about 1%, about 0.2% and about 0.8%, about 0.4 and about 0.6%, 1% and 2%, about 1.2% and about 1.8%, about 1.4% and about 1.6%; b) between 0% and 2%, 0.2% and 1.8%, 0.4% and 1.6%, 0.6% and 1.4%, 0.8% and 1.2%, 0% and 1%, 0.2% and 0.8%, 0.4 and 0.6%, 1% and 2%, 1.2% and 1.8%, 1.4% and 1.6%; c) below about 2%, below about 1.5%, below about 1.6%, below about 1.4%, below about 1.2%, below about 1%, below about 0.8%, below about 0.6%, below about 0.4%, below about 0.2% or lower; d) below 2%, below 1.5%, below 1.6%, below 1.4%, below 1.2%, below 1%, below 0.8%, below 0.6%, below 0.4%, below 0.2% or lower; e) about 2%, about 1.8%, about 1.6%, about 1.4%, about 1.2%, about 1%, about 0.8%, about 0.6%, about 0.4%, about 0.2%; and / or f) 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.4%, 0.2%. 12. The recombinant bacterial cell of paragraph 10 or 11, wherein the hypoxia-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide in normoxia; optionally wherein the hypoxia-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) above about 6%, above about 5%, above about 4%, or above about 3%; b) above 6%, above 5%, above 4%, or above 3%; c) about 6%, about 5%, about 4%, about 3%; and / or d) 6%, 5%, 4%, 3%. 13. The recombinant bacterial cell of any of paragraphs 10-12, wherein the hypoxia- inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide when the recombinant cell is incubated in culture media under mineral oil, optionally incubated at 37°C for 18 hours. 14. The recombinant bacterial cell of any of paragraphs 10-13, wherein: a) the hypoxia-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; and / or b) the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 15. The recombinant bacterial cell of paragraph 9, wherein the inducible promoter is a pH-inducible promoter; optionally wherein the pH inducible promoter is selected from the group comprising or consisting of: LPR7, LPR1, LPR9, Stm1787, hyaA, P1, P2, and P3. 16. The recombinant bacterial promoter of paragraph 15, wherein the pH-inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.5 and about pH 7, about pH 5.6 and about pH 6.9, about pH 5.7 and about pH 6.8, about pH 5.8 and about pH 6.7, about pH 5.9 and about pH 6.6, about pH 6.0 and about pH 6.5, about pH 6.1 and about pH 6.4, about pH 6.2 and about pH 6.3; b) between pH 5.5 and pH 7, pH 5.6 and pH 6.9, pH 5.7 and pH 6.8, pH 5.8 and pH 6.7, pH 5.9 and pH 6.6, pH 6.0 and pH 6.5, pH 6.1 and pH 6.4, pH 6.2 and pH 6.3 c) below about pH 7, below about pH 6.9, below about pH 6.8, below about pH 6.7, below about pH 6.6, below about pH 6.5, below about pH 6.4, below about pH 6.3, below about pH 6.2, below about pH 6.1, below about pH 6.0, below about pH 5.9, below about pH 5.8, below about pH 5.7, below about pH 5.6, or lower; d) below pH 7, below pH 6.9, below pH 6.8, below pH 6.7, below pH 6.6, below pH 6.5, below pH 6.4, below pH 6.3, below pH 6.2, below pH 6.1, below pH 6.0, below pH 5.9, below pH 5.8, below pH 5.7, below pH 5.6; e) about pH 5.5, about pH 5.6, about pH 5.7, about pH 5.8, about pH 5.9, about pH 6.0, about pH 6.1, about pH 6.2, about pH 6.3, about pH6.4, about pH 6.5, about pH 6.6, about pH 6.7, about pH 6.8, about pH 6.9, or about pH 7; and / or f) pH 5.5, pH 5.6, pH 5.7, pH 5.8, pH 5.9, pH 6.0, pH 6.1, pH 6.2, pH 6.3, pH6.4, pH 6.5, pH 6.6, pH 6.7, pH 6.8, pH 6.9, or pH 7. 17. The recombinant bacterial promoter of paragraph 15 or 16, wherein the pH- inducible promoter is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH; optionally wherein the acidic pH is: a) between about pH 5.9 and about pH 6.5, about pH 5.95 and about pH 6.45, about pH 6.0 and about pH 6.4, about pH 6.05 and about pH 6.35, about pH 6.1 and about 6.3, or about pH 6.15 and about pH 6.25; b) between pH 5.9 and pH 6.5, pH 5.95 and pH 6.45, pH 6.0 and pH 6.4, pH 6.05 and pH 6.35, pH 6.1 and 6.3, or pH 6.15 and pH 6.25; c) about pH 5.9, about pH 5.95, about pH 6.0, about pH 6.05, about pH 6.1, about pH 6.15, about pH 6.2, about pH 6.25, about pH 6.3, about pH 6.35, about pH 6.4, about pH 6.45, or about pH 6.5; and / or d) pH 5.9, pH 5.95, pH 6.0, pH 6.05, pH 6.1, pH 6.15, pH 6.2, pH 6.25, pH 6.3, pH 6.35, pH 6.4, pH 6.45, or pH 6.5. 18. The recombinant bacterial cell of any of paragraphs 15-17, wherein: a) the pH-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; and / or b) the pH-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, or SEQ ID NO: 61; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, or SEQ ID NO: 60, or SEQ ID NO: 61. 19. The recombinant bacterial cell of any of paragraphs 15-18, wherein the pH-inducible promoter is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an alkaline pH. 20. The recombinant bacterial cell of paragraphs 9-19, wherein the inducible promoter is a pH-inducible and / or hypoxia-inducible promoter; optionally wherein the pH-inducible and hypoxia-inducible promoter is LOR9; optionally wherein: a) the LOR9 promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 73, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 73; and / or b) the LOR9 promoter is encoded by a nucleotide sequence of SEQ ID NO: 55 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 55. 21. The recombinant bacterial cell of any of paragraphs 10-14 and 20, wherein the hypoxia-inducible promoter comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding sequence; a modified operator sequence; or any combination thereof. 22. The recombinant bacterial cell of any of paragraphs 15-19 and 20, wherein the pH- inducible promoter comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding sequence; a modified operator sequence; or any combination thereof. 23. The recombinant bacterial cell of any of paragraphs 1-22, wherein the heterologous extracellular matrix (ECM) degrading polypeptide: a) is secreted from the cell; b) is displayed on the surface of the cell; or c) is expressed in the cell. 24. The recombinant bacterial cell of paragraphs 1-23, wherein the heterologous extracellular matrix (ECM) degrading polypeptide is secreted from the cell. 25. The recombinant bacterial cell of paragraphs 1-24, wherein the heterologous extracellular matrix (ECM) degrading polypeptide is a fusion polypeptide comprising: a) an ECM degrading domain; and b) a secretion domain; optionally wherein the heterologous extracellular matrix (ECM) degrading polypeptide comprises two secretion domains; and optionally c) a cleavage domain; optionally wherein the cleavage domain is positioned between the ECM degrading domain and the secretion domain. 26. The recombinant bacterial cell of paragraphs 24 or 25, wherein: a) the secretion domain is selected from the group comprising or consisting of: a PelB secretion signal sequence, a YebF carrier protein, a CtxB signal sequence, an AIDA-I autotransporter, a FliC signal sequence, and a Usp45 signal sequence, or any combination thereof; and / or b) the cleavage domain comprises a matrix metalloprotease (MMP) cleavage site. 27. The recombinant bacterial cell of any of paragraphs 24-26, wherein: i) the secretion domain: a) comprises or consists of an amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36; and / or ii) the cleavage domain: a) comprises or consists of an amino acid sequence of SEQ ID NO: 116; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 116; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 117, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 117. 28. The recombinant bacterial cell of any of paragraphs 24-27, wherein the fusion polypeptide: a) comprises an ECM degrading domain that comprises a hyaluronidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46; or b) comprises an ECM degrading domain that comprises a neuraminidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114or an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, or SEQ ID NO: 114; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, or SEQ ID NO: 115. 29. The recombinant bacterial cell of any of paragraphs 2-28, wherein the nucleic acid further comprises a nucleotide sequence encoding a transcriptional regulatory polypeptide. 30. The recombinant bacterial cell of paragraph 29, wherein where the secretion domain is a FliC signal sequence, the transcriptional regulatory peptide is selected from the group comprising or consisting of: a FliC repressor; optionally wherein the FliC repressor is a GadE repressor. 31. The recombinant bacterial cell of paragraph 30, wherein the transcriptional regulatory peptide: a) comprises or consists of an amino acid sequence of SEQ ID NO: 49; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 49; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 50, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 50. 32. The recombinant bacterial cell of any of paragraphs 1-31, wherein the cell is a non- pathogenic bacterial cell, a commensal cell, or a probiotic cell. 33. The recombinant bacterial cell of any of paragraphs 1-32, wherein the cell is a facultatively anaerobic cell. 34. The recombinant bacterial cell of any of paragraphs 1-33, wherein the cell is: a) a gram-negative bacterial cell; or b) a gram-positive bacterial cell. 35. The recombinant bacterial cell of paragraph 34, wherein the gram-negative bacterial cell is selected from the group comprising or consisting of: an Escherichia coli cell; optionally wherein the gram-negative bacterial cell is an Escherichia coli K12 cell; optionally wherein the Escherichia coli K12 cell is Escherichia coli K12 MG1655 cell. 36. The recombinant bacterial cell of paragraph 34, wherein the gram-positive bacterial cell is a lactic acid bacterial cell; optionally wherein the lactic acid bacterial cell is selected from the group comprising or consisting of: a Lactococcus lactis cell, a Lactobacillus cell, and a Bifidobacterium cell optionally wherein the gram-positive bacterial cell is a Lactococcus lactis MG1363 cell. 37. The recombinant bacterial cell of any of paragraphs 1-36, wherein the cell is not an attenuated bacterial cell. 38. The recombinant bacterial cell of any of paragraphs 1-37, wherein the cell is not: a) a Salmonella cell; optionally a Salmonella bongori cell, a Salmonella cholreaesuis cell, a Salmonella enterica cell, a Salmonella enteritidis cell, a Salmonella paratyphi cell, a Salmonella typhi cell, or a Salmonella typhimurium cell; b) a Vibrio cell; optionally a Vibrio cholerae cell or a Vibrio fischeri cell; c) a Shigella cell; optionally a Shigella boydii cell, a Shigella dysenteriae cell, a Shigella flexneri cell, or a Shigella sonnei cell; d) a Lactobacillus cell; optionally a Lactobacillus bulgaricus cell; e) a Listeria cell; optionally a Listeria monocytogenes cell; f) an Enterococcus cell; optionally an Enterococcus faecium cell; g) a Streptococcus cell; optionally a Streptococcus pyogenes cell; and / or h) a pathogenic Escherichia coli cell; optionally an Enteroinvasive Escherichia coli (EIEC) cell, an Adherent-Invasive Escherichia coli (AIEC) cell, an Enteroaggregative Escherichia coli (EAEC) cell, a Shiga Toxin-producing Escherichia coli (STEC) cell, an Enterotoxigenic Escherichia coli (ETEC) cell, or an Enterohemorrhagic Escherichia coli (EHEC) cell. 39. The recombinant bacterial cell of any of paragraphs 1-38, wherein the heterologous extracellular matrix (ECM) degrading polypeptide does not localise to an intracellular compartment of the cell. 40. The recombinant bacterial cell of any of paragraphs 1-39, wherein the heterologous extracellular matrix (ECM) degrading polypeptide does not localise to a membrane or cell wall of the cell. 41. The recombinant bacterial cell of any of paragraphs 2-40, wherein the nucleic acid further comprises a nucleotide sequence encoding a transcriptional regulatory element. 42. The recombinant bacterial cell of paragraph 41, wherein the nucleotide sequence encoding the heterologous extracellular matrix degrading (ECM) polypeptide is operably linked to the transcriptional regulatory element. 43. The recombinant bacterial cell of paragraphs 41-42, wherein the transcriptional regulatory element is selected from the group comprising or consisting of: a terminator sequence, a repressor binding sequence, an insulator, an operator sequence, or any combination thereof. 44. The recombinant bacterial cell of paragraph 43, wherein: a) the terminator is selected from the group comprising or consisting of: rrnB T1 / T2; optionally wherein the terminator sequence has a sequence of SEQ ID NO: 51; b) the repressor binding sequence is selected from the group comprising or consisting of: FNR; optionally wherein the repressor binding sequence has a sequence of SEQ ID NO: 52; and / or c) the insulator sequence is selected from the group comprising or consisting of: RiboJ; optionally wherein the insulator sequence has a sequence of SEQ ID NO: 53. 45. The recombinant bacterial cell of any of paragraphs 2-44, wherein the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC); optionally wherein the nucleic acid is a plasmid. 46. The recombinant bacterial cell of any of paragraphs 2-44, wherein the nucleic acid integrated into the genome of the cell. 47. The recombinant bacterial cell of any of paragraphs 1-46, wherein the cell is capable of accumulating in a target tissue or tumour. 48. A hypoxia-inducible promoter, wherein the hypoxia-inducible promoter is a promoter according to any of paragraphs 10-14 and 20, optionally wherein the hypoxia- inducible promoter is an engineered hypoxia-inducible promoter. 49. The hypoxia-inducible promoter of paragraph 48, wherein: a) the hypoxia-inducible promoter is an LOR9, an LOR7 promoter, or an LOR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 50. A pH-inducible promoter, wherein the pH-inducible promoter is a promoter according to any of paragraphs 15-19 and 21, optionally wherein the pH-inducible promoter is an engineered pH-inducible promoter. 51. The pH-inducible promoter of paragraph 50, wherein: a) the pH-inducible promoter is an LPR9, an LPR7 promoter, or an LPR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO: 59; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO: 59. 52. A nucleic acid comprising a nucleotide sequence of the hypoxia-inducible promoter of paragraphs 48-49 and / or the pH-inducible promoter of paragraph 50-51. 53. A nucleic acid comprising a nucleotide sequence encoding an extracellular matrix (ECM) degrading polypeptide. 54. The nucleic acid of paragraph 53, wherein the extracellular matrix (ECM) degrading polypeptide is the heterologous extracellular matrix (ECM) degrading polypeptide according to any of paragraphs 1-6 and 19-28. 55. The nucleic acid of paragraph 53 or 54, wherein the nucleic acid further comprises a promoter; optionally wherein the promoter is the promoter of any of paragraphs 7-18 and 48-51. 56. The nucleic acid of paragraph 55, wherein the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the promoter. 57. The nucleic acid of any of paragraphs 52-56, further comprising a transcriptional regulatory element; optionally wherein the transcriptional regulatory element is the transcriptional regulatory element of any of paragraphs 41-44-. 58. The nucleic acid of paragraph 57, wherein the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the transcriptional regulatory element. 59. The nucleic acid of any of paragraphs 52-58, wherein the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC); optionally wherein the nucleic acid is a plasmid. 60. A cell comprising the engineered hypoxia-inducible promoter of any of paragraphs 48-49, the engineered pH-inducible promoter of any of paragraphs 50-51, and / or the nucleic acid of any of paragraphs 52-59. 61. The cell of paragraph 60, wherein the nucleic acid is: a) extrachromosomal; or b) integrated into the genome of the cell. 62. The cell of paragraphs 60-61, wherein the cell is a recombinant bacterial cell; optionally wherein the cell is a recombinant bacterial cell according to any of paragraphs 1-47. 63. The recombinant bacterial cell of any of paragraphs 1-47 for use in medicine. 64. The recombinant bacterial cell of any of paragraphs 1-47 for use as a medicament. 65. The recombinant bacterial cell of any of paragraphs 1-47 for use in treating cancer. 66. The cell of any of paragraphs 60-62 for use in medicine. 67. The cell of any of paragraphs 60-62 for use as a medicament. 68. The cell of any of paragraphs 60-62 for use in treating cancer. 69. The recombinant bacterial cell for use of any of paragraphs 63-65 or cell for use of any of paragraphs 66-68, wherein the use comprises administering an effective dose of the cell to a subject that has cancer. 70. The recombinant bacterial cell for use according to paragraph 65 or 69, or the cell for use of any of paragraph 68 or 69, wherein the cancer is a tumour solid cancer, optionally wherein the cancer is an immune-excluded solid tumour cancer and / or an immune- excluded tumour. 71. The recombinant bacterial cell for use according to paragraph 65, 69, or 70, or cell for use according to any of paragraphs 68-70, wherein: a) the cancer is a cancer that comprises extracellular matrix; optionally wherein the cancer is selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer; and / or b) the cancer is not a cancer that does not comprise extracellular matrix; optionally wherein the cancer is not a blood cancer; optionally wherein the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, and lymphoma. 72. A composition comprising the recombinant bacterial cell of paragraphs 1-47 or the cell of paragraphs 60-62, optionally wherein the composition is a pharmaceutical composition. 73. The composition of paragraph 72 for use in medicine. 74. The composition of paragraph 72 for use as a medicament. 75. The composition of paragraph 72 for use in a method of treating cancer. 76. The composition for use of any of paragraphs 73-75, wherein the use comprises administering an effective dose of the composition to a subject. 77. The composition for use of any of paragraphs 73-76, wherein the cancer is a solid tumour cancer, optionally wherein the cancer is an immune-excluded solid cancer. 78. The composition for use of any of paragraphs 73-77, wherein the cancer is a cancer selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer. 79. A method for degrading extracellular matrix (ECM) in a tissue, comprising contacting the tissue with the recombinant bacterial cell of any of paragraphs 1-47, the cell of paragraphs 60-61, or the composition of paragraph 72. 80. The method of paragraph 79, wherein the method is an in vivo method. 81. The method of paragraph 79 or 80, wherein the method comprises administering the recombinant bacterial cell, the cell, or the composition to a subject. 82. The method of paragraph 81, wherein the subject has a disease. 83. The method of paragraph 82, wherein the disease is cancer; optionally wherein the cancer is a solid tumour cancer, optionally wherein the cancer is an immune-excluded solid cancer. 84. The method of paragraph 83, wherein: a) the cancer is a cancer that comprises extracellular matrix; optionally wherein the cancer is selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer; and / or b) the cancer is not a cancer that does not comprise extracellular matrix; optionally wherein the cancer is not a blood cancer; optionally wherein the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, and lymphoma. 85. The method of paragraph 79, wherein the method is an in vitro method. 86. The recombinant bacterial cell for use of any of paragraphs 63-65, 69-71, cell for use of any of paragraphs 66-71, composition for use of any of paragraphs 73-78, or the method of any of paragraphs 79-85, wherein the subject is a human subject. 87. Use of the recombinant bacterial cell of any of paragraphs 1-47 the cell of paragraphs 60-62, or the composition of paragraph 72 to degrade extracellular matrix (ECM). 88. Use of paragraph 87, wherein the use is an in vitro use or an in vivo use. 89. Use of paragraphs 87-88, wherein the use comprises administering the recombinant bacterial cell, the cell, or the composition to a subject. 90. The recombinant bacterial cell for use of any of paragraphs 63-65, 69-71 and 86, cell for use of any of paragraphs 66-71 or 86, composition for use of any paragraphs 73- 78 and 86, method of any of paragraphs 79-86, or use of any of paragraphs 87-89, wherein the recombinant bacterial cell, the cell, or the composition is administered to a subject by a route selected from the group comprising or consisting of: oral administration, intraocular administration, intravenous administration, intraarterial administration, intraperitoneal administration, intramuscular administration, intratumoural administration, buccal administration, nasal administration, pulmonary administration. 91. The recombinant bacterial cell for use, composition for use, method, or use of paragraph 90, wherein following administration the recombinant bacterial cell or cell accumulates in a target tissue or tumour in the subject. 92. The recombinant bacterial cell for use, composition for use, method, or use of paragraph 91, wherein the recombinant bacterial cell or cell degrades the extracellular matrix (ECM) of the target tissue or tumour. 93. The recombinant bacterial cell for use of any of paragraphs 63-65, 69-71, 86 and 90-92, cell for use of any of paragraphs 66-71, 86, and 90-92, composition for use of any of paragraphs 73-78, 86, and 90-92, method of any of paragraphs 79-86, 90-92, or use of any of paragraphs 87-92, 76-77, wherein the recombinant bacterial cell, cell, or composition is: a) administered prior to or subsequent to administration of a cancer therapeutic; and / or b) co-administered with a cancer therapeutic. 94. The recombinant bacterial cell for use, composition for use, method, or use of paragraph 93, wherein the cancer therapeutic is selected from the group comprising or consisting of: a) an antibody (optionally selected from the group comprising or consisting of: an immune checkpoint inhibitor (ICI), T-cell engager, and a bispecific antibody or an antibody-drug conjugate), a cell therapy (optionally selected from the group comprising or consisting of: a T-cell, a CAR-T cell, and a T4 cell), a chemotherapy agent (optionally selected from the group comprising or consisting of: FOLFOX, Gemcitabine, Paclitaxel, Cisplatin, Epirubicin and Irinotecan) an Immunomodulator (optionally selected from the group comprising or consisting of: a cytokine and a chemokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), and a second live biotherapeutic (optionally selected from the group comprising or consisting of: an engineered live biotherapeutic and a recombinant bacterial cell); and / or b) an antibody (optionally an immune checkpoint inhibitor antibody, bispecific antibody or an antibody-drug conjugate), a hormonal therapy, a targeted therapy, an immunotherapy, a cell therapy (optionally a tumour infiltrating lymphocyte (TIL), a lymphocyte with an engineered T cell receptor (TCR), a CAR T cell, or a Natural Killer cell), an immunomodulator (optionally a chemokine or a cytokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), another luve biotherapeutic (optionally an engineered live biotherapeutic), a chemotherapy (optionally an alkylating agent (optionally temozolomide and carboplatin), an anti- metabolite (optionally 5-FU or gemcitabine), an anti-tumour antibiotic (optionally doxorubicin), a topoisomerase inhibitor (optionally irinotecan), a mitotic inhibitor (optionally a taxane, like paclitaxel or docetaxel), a corticosteroid (optionally dexamethasone). 95. A pharmaceutical composition comprising the recombinant bacterial cell of any of paragraphs 1-47 or the cell of any of paragraphs 60-62, and a cancer therapeutic, for use in treating cancer. 96. A combination comprising the recombinant bacterial cell of any of paragraphs 1-47 or cell of paragraphs 60-62 and a cancer therapeutic for use in treating cancer. 97. A combination comprising a cancer therapeutic and the recombinant bacterial cell of any of paragraphs 1-47 or cell of paragraphs 60-62 for use in treating cancer. 98. The pharmaceutical composition for use of paragraph 95, or combination for use of paragraph 96 or 97, wherein: a) the cancer is a cancer that comprises extracellular matrix; optionally wherein the cancer is selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer; and / or b) the cancer is not a cancer that does not comprise extracellular matrix; optionally wherein the cancer is not a blood cancer; optionally wherein the cancer is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, and lymphoma. 99. The pharmaceutical composition for use of paragraphs 95 or 98, or combination for use of any of paragraphs 96-98, wherein the cancer therapeutic is a cancer immunotherapy agent, optionally wherein the cancer immunotherapy agent is selected from the group comprising or consisting of: a) an antibody (optionally selected from the group comprising or consisting of: an immune checkpoint inhibitor (ICI), T-cell engager, and a bispecific antibody or an antibody-drug conjugate), a cell therapy (optionally selected from the group comprising or consisting of: a T-cell, a CAR-T cell, and a T4 cell), a chemotherapy agent (optionally selected from the group comprising or consisting of: FOLFOX, Gemcitabine, Paclitaxel, Cisplatin, Epirubicin and Irinotecan) an Immunomodulator (optionally selected from the group comprising or consisting of: a cytokine and a chemokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), and a second live biotherapeutic (optionally selected from the group comprising or consisting of: an engineered live biotherapeutic and a recombinant bacterial cell); and / or b) an antibody (optionally an immune checkpoint inhibitor antibody, bispecific antibody or an antibody-drug conjugate), a hormonal therapy, a targeted therapy, an immunotherapy, a cell therapy (optionally a tumour infiltrating lymphocyte (TIL), a lymphocyte with an engineered T cell receptor (TCR), a CAR T cell, or a Natural Killer cell), an immunomodulator (optionally a chemokine or a cytokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), another live biotherapeutic (optionally an engineered live biotherapeutic), a chemotherapy (optionally an alkylating agent (optionally temozolomide and carboplatin), an anti- metabolite (optionally 5-FU or gemcitabine), an anti-tumour antibiotic (optionally doxorubicin), a topoisomerase inhibitor (optionally irinotecan), a mitotic inhibitor (optionally a taxane, like paclitaxel or docetaxel), a corticosteroid (optionally dexamethasone). 100. The composition for use of any of paragraphs 95, 98, or 99, or combination for use of any of paragraphs 96-99, wherein the recombinant bacterial cell or cell is administered to a subject; optionally wherein: a) the recombinant bacterial cell or cell is administered prior to or subsequent to administration of the cancer therapeutic; and / or b) the recombinant bacterial cell or cell is co-administered with the cancer therapeutic. 101. The composition for use of any of paragraphs 95 or 98-100, or combination for use of any of paragraphs 96-100, wherein the composition or combination for use is administered to a subject by a route selected from the group comprising or consisting of: oral administration, intraocular administration, intravenous administration, intraarterial administration, intraperitoneal administration, intramuscular administration, intratumoural administration, buccal administration, nasal administration, pulmonary administration. 102. The composition for use of any of paragraphs 95 or 98-101, or combination for use of any of paragraphs 96-101, wherein following administration the recombinant bacterial cell or cell accumulates in a target tissue or tumour in the subject. 103. The composition for use or combination for use of paragraph 102, wherein the recombinant bacterial cell or cell degrades the extracellular matrix (ECM) of the target tissue or tumour. 104. The recombinant bacterial cell for use, composition for use, method, or use of paragraph 93, or the composition for use or combination for use of paragraph 103, wherein the degradation of the extracellular matrix (ECM) of the target tissue or tumour allows the cancer therapeutic to contact and / or enter the tumour; optionally wherein said contacting and / or entering the tumour is required for the therapeutic effect of the cancer therapeutic. 105. A kit of parts, comprising: a) the recombinant bacterial cell of any of paragraphs 1-39; b) the engineered hypoxia-inducible promoter of paragraph 40; c) the engineered pH-inducible promoter of paragraph 41; d) the nucleic acid of any of paragraphs 42-49; e) the cell of any of paragraphs 50-59; f) the composition of any of paragraphs 61-64; g) a therapeutic agent, optionally an anti-cancer therapeutic. Figure legends Figure 1 – A) Luminescence measurement of luminescent E. coli K12 MG1655 using Photoimager Optima In Vivo Imaging System, showing successful generation of a luminescent strain. B) Bodyweight of mice administered luminescent E. coli K12 MG1655 intravenously at doses of 106, 107, and 108CFU, heat-killed bacteria, or vehicle only. Figure 2 - Bioluminescence imaging using Photoimager Optima In Vivo Imaging System, showing localisation of luminescent E. coli K12 MG1655 to tumours in the mice. Figure 3 – A) Bioluminescence imaging using Photoimager Optima In Vivo Imaging System, showing localisation of luminescent E. coli K12 MG1655 to tumours in the mice. B) Quantification of the bacterial load by CFU in four tissue samples (liver, spleen, heart, and tumour) of 8 mice, showing accumulation of E. coli K12 MG1655 to tumours. Figure 4 - Functional analysis of Escherichia coli K12 MG1655 PelB-bH. Error bars = standard error of the mean. All data are representative of ≥3 experiments. Figure 5 – Bacterial invasion in patient derived tissue samples. Bacteria expressing GFP are green (white) and identified with white arrows; and ECM is blue (grey). Figure 6 – Degradation of hyaluronic acid (HA) in patient explant tissue by Escherichia coli K12 MG1655 PelB-bH. IHC staining of HA. Untreated tissue represents tissue incubated with media only. Figure 7 - HA degradation by bH- expressing bacteria has synergistic effects with CAR-T cell mediated killing of cancer cells in patient derived tissue explants. Bar chart showing the relative cell killing by each treatment arm in the assay. Figure 8 – ECM degradation by secreted bacterial enzymes. A) Functional analysis of secreted bacterial hyaluronidase. Bar chart showing the level of hyaluronic acid in the media after each treatment arm in the assay. B) Western blot against an amino terminal Flag-tag fused to bHs. Predicted bHs size ~90 kDa (arrow). Ctrl - no induction. Rh - Induced with Rhamnose. GFP- Bacteria expressing GFP. 1B - bacteria expressing bacterial hyaluronidase. Error bars = standard error of the mean. All data are representative of ≥3 experiments. C) Level of neuraminidase activity secreted by E. coli K12 MG1655 PelB-Nh. Negative control E.coli K12 MG1655 GFP. Error bars = standard error of the mean. All data are representative of ≥3 experiments. D) Secretion system evaluation by measuring neuraminidase as payload with Neuraminidase assay kit (Abcam, UK). Bar chart showing the level of neuraminidase (NH) in the media after each treatment arm in the assay. Evec = no payload. MMP = Cleavage site to release payload for YebF, FliC and AidaC secretion system. Error bars = standard error of the mean. All data are representative of ≥3 experiments. Figure 9 – A) and B) GFP fluorescence level in Normoxia and Hypoxia conditions at pH 7 and pH 6. GFP = positive control E. coli K12 MG1655 constitutively expressing GFP. LO / LP R7, R9, R1 = E. coli K12 MG1655 expressing GFP under engineered hypoxia inducible promoters. The level of fluorescence was corrected using E. coli K12 MG1655 expressing non-fluorescent protein under the control of rhamnose inducible promoter. Error bars = standard error of the mean. C) HA degradation by secreted bacterial hyaluronidase in Normoxia and Hypoxia conditions at pH 7 and pH 6. 1B+ = E. coli K12 MG1655 expressing bacterial hyaluronidase under control of a rhamnose-inducible promoter, induced with 0.2% of rhamnose. LOR7, R9 = E. coli K12 MG1655 expressing GFP under control of engineered hypoxia inducible promoters. The level of degradation was corrected using E. coli K12 MG1655 constitutively expressing a fluorescent protein. Error bars = standard error of the mean. Figure 10 – Treatment of mice bearing 4T1 breast tumors with E. coli K12 MG1655 expressing Hyaluronidase under the control of LOR7 and LOR9 promoter reduces tumor stiffness in just 3 days post-administration as indicated by ultrasound shear wave elastography (SWE) measurements (A) and a significant degradation of hyaluronan levels in the TME (C). Vascular perfusion measured by contrast enhanced ultrasound (CEUS) is also improved upon E. coli-HAse administration (B). Error bars = standard error of the mean. N = 6 mice. Figure 11 – E. coli K12 MG1655 expressing hyaluronidase under control of the LO R7 promoter enhances immunotherapy efficacy in triple-negative breast cancer murine models. Tumor growth curves of orthotopic (A) 4T1 and (B) E0771 tumors treated as indicated (n=7-10 mice per treatment group). E. coli expressing hyaluronidase under the control of the LO R7 promoter (LO R7 cells) at a dose of 106CFUs were administered by an i.v. injection once the tumors reached an average size of 150 mm3, followed by three cycles of the immunotherapy cocktail consisting of 10 mg / kg anti-PD-1 and 5 mg / kg anti- CTLA-4 (ICI, immune checkpoint inhibitors). Data are presented as mean ± SE. Statistical analyses were performed by comparing means between independent groups using the two- way ANOVA test (For the 4T1 study: PBS vs. LO R7, p= 0.0004; LO R7 vs. LO R7+ICI, p=0.0045; ICI vs. LO R7+ICI, p=0.0007. For the E0771 study: PBS vs. ICI, p=0.036; PBS vs. LO R7+ICI, p=0.0008; LO R7 vs. ICI, p=0.0199; LO R7 vs. LO R7+ICI, p=0.0016; ICI vs. LO R7+ICI, p=0.0401). Figure 12 – Survival curves of 4T1 and E0771 tumour models. Survival curves of orthotopic (A) 4T1 and (B) E0771 tumors treated as indicated (n=7-10 mice per treatment group). Figure 13 – (A-G) Flow cytometry analysis of 4T1 tumors. (A) Percentage of CD45+lymphocytes amongst live cells of 4T1 tumors treated as indicated. (B) Percentage of the myeloid-derived suppressor cell (MDSC) population defined as CD45+GR1+CD11b+and (C) tumor-associated macrophages (TAMs) defined as CD45+GR1-CD11b+F4 / 80+amongst lymphocytes. (D) Ratio of immunosupportive M1-like TAMs (CD45+GR1- CD11b+F4 / 80+CD38+CD206-) to immunosuppressive M2-like TAMs (CD45+GR1- CD11b+F4 / 80+CD38-CD206+). (E) Percentage of CD4+T cells (CD3+CD4SP+) and (F) CD8+T cells (CD3+CD8SP+) gated on lymphocytes. (G) Ratio of cytotoxic CD8+T cells to regulatory T cells defined as CD3+CD4SP+CD25hiCD127loFoxp3+(n=7-10 mice per treatment group). (H-N) Flow cytometry analysis of E0771 tumors. (H) Percentage of CD45+lymphocytes amongst live cells. (I) Percentage of MDSCs and (J) TAMs gated on lymphocytes. (K) Ratio of M1- to M2-like TAMs. (L) Percentage of CD4+T cells (TCRB+CD4SP+) and (M) CD8+T cells (TCRB+CD8SP+) gated on lymphocytes. (N) Ratio of cytotoxic CD8+T cells to T regs (n=7-10 mice for PBS, LO R7 and ICI treatment groups and n=4 for LO R7+ICI combination group due to complete tumor regression, which occurred in 5 out of 10 mice included in this group). Data are presented as mean ± SE. Statistical analyses were performed by comparing means between independent groups using the one-way ANOVA test. Sequences referred to herein SEQ_ID_NO:_1_Bacterial_HA_AA MTYRIKKWQKLSTITLLMAGVITLNGGEFRSVDKHQIAVADTNVQTPDYEKLRNTWLDVNYGYDKYDENNPDMKKKFDATEKEATNLLKEMKTESGRKYLWSGAETLETNSSHMTRTYRNIEKIAEAMRNPKTTLNTDENKKKVKDALEWLHKNAYGKEPDKKVKELSENFTKTTGKNTNLNWWDYEIGTPKSLTNTLILLNDQFSNEEKKKFTAPIKTFAPDSDKILSSVGKAELAKGGNLVDISKVKLLECIIEEDKDMMKKSIDSFNKVFTYVQDSATG KERNGFYKDGSYIDHQDVPYTGAYGVVLLEGISQMMPMIKETPFNDKTQNDTTLKSWIDDGFMPLIYKGEMMDLSRGRAISRENETSHSASATV MKSLLRLSDAMDDSTKAKYKKIVKSSVESDSSYKQNDYLNSYSDIDKMKSLMTDNSISKNGLTQQLKIYNDMDRVTYHNKDLDFAFGLSMTSKN VARYESINGENLKGWHTGAGMSYLYNSDVKHYHDNFWVTADMKRLSGTTTLDNEILKDTDDKKSSKTFVGGTKVDDQHASIGMDFENQDKTLTA KKSYFILNDKIVFLGTGIKSTDSSKNPVTTIENRKANGYTLYTDDKQTTNSDNQENNSVFLESTDTKKNIGYHFLNKPKITVKKESHTGKWKEI NKSQKDTQKTDEYYEVTQKHSNSDNKYGYVLYPGLSKDVFKTKKDEVTVVKQEDDFHVVKDNESVWAGVNYSNSTQTFDINNTKVEVKAKGMFI LKKKDDNTYECSFYNPESTNSASDIESKISMTGYSITNKNTSTSNESGVHFELTK >SEQ_ID_NO:_2_Bacterial_HA_DNA atgacatatagaataaagaaatggcaaaaattatccaccattacgttattaatggctggtgtgattactttgaatggtggtgaattcagaagtg ttgataaacatcaaatcgctgtggctgatacgaatgttcaaacgccagattatgaaaaattgaggaacacatggctggacgttaactatggtta tgataagtatgatgagaataatccagatatgaagaagaagtttgatgctacagagaaagaggcgacgaatttactcaaggaaatgaaaactgaaagtggtaggaaatacttgtggtcaggagcggaaacccttgaaactaattcttctcatatgactcgtacctatcgtaatattgagaaaatcgcagaagcgatgaggaatcctaaaaccactttaaatactgacgaaaataagaagaaagtgaaagatgcccttgagtggctgcataaaaatgcatatgg aaaagaaccagataaaaaagtaaaagaattaagtgagaattttactaaaacaactggcaagaataccaacttaaattggtgggattatgaaatt ggaacacctaaatcattaacaaatacgcttatattgctgaatgatcaattttcaaatgaagaaaagaaaaaattcactgcccctattaaaactt tcgccccagatagtgacaaaatattatcttctgtaggaaaagctgaacttgctaaaggcggaaatctagtagacatttctaaggtgaaactttt agaatgtattatcgaagaagataaagatatgatgaaaaagtctatagattcatttaataaagtcttcacttacgttcaagattctgccactggt aaagaacgtaatggattttataaagatggctcttacattgatcatcaagacgttccatacactggtgcttatggcgttgtactcttagagggga tttctcaaatgatgccgatgataaaagaaacaccttttaatgataaaacccaaaatgatacaaccttaaagtcatggattgacgacggatttat gccactcatttataaaggtgaaatgatggatttatcacgaggtagagctatcagtcgtgaaaatgaaaccagtcactcagcatctgcaacagta atgaaatcattgttgagattaagtgatgccatggatgattcaacaaaagctaagtataaaaagattgtcaaatcttcagtagagtcagattcaa gttataaacaaaatgattatttaaattcatattcggacatagataaaatgaagtctttaatgacagataacagtatttctaaaaacggattaac acaacaacttaaaatatataatgacatggatcgtgtcacctatcataacaaagacttagactttgcatttggtttaagtatgacgtcgaaaaac gtagcacgctatgaaagtatcaacggagagaatttaaaaggttggcacactggtgctggaatgtcttatttatataacagcgatgtcaaacact atcatgataacttctgggtgacagccgatatgaaacgtttatcaggtacaacaactttagacaatgaaatattaaaagatacggatgataaaaa gtcgagtaaaacttttgttggcggaacaaaagttgatgaccaacatgctagtatcggaatggattttgaaaatcaggacaaaactttaactgcc aaaaaatcatatttcatattaaacgataaaattgtcttcttaggaactggcattaaaagtactgattcatcaaagaatccagttacaacgattg aaaatcgcaaagcgaatgggtatacgttatatacagacgataaacaaacaaccaattctgataatcaggaaaacaattcagtctttttagagtc cacagataccaaaaagaacatcggttatcattttttaaacaaaccgaaaataactgtaaaaaaagaaagtcatactggtaagtggaaagaaata aataaaagtcaaaaggatacacaaaaaactgatgagtattatgaagtaactcaaaagcattctaattctgacaataaatatggatatgtgttgt atccaggcttatctaaagatgtctttaagacaaaaaaagatgaagtaactgtcgttaagcaagaagatgacttccacgttgtgaaagataatga atcggtttgggctggtgttaattatagtaatagcactcaaacttttgacattaacaacactaaagtcgaagttaaagccaaaggtatgtttata cttaaaaagaaagatgataacacttatgaatgtagcttctataatcctgaatctacaaattccgcttcagatattgaatctaaaatttcaatga ccggttactctattacaaacaaaaatacgtcgacttctaatgaatccggcgtgcactttgaattaactaaataa >SEQ_ID_NO:_3_chondroitin_ABC_lyase_AA MKKKIISAILMSTVILSAAAPLSGVYAATSNPAFDPKNLMQSEIYHFAQNNPLADFSSDKNSILTLSDKRSIMGNQSLLWKWKGGSSFTLHKKL IVPTDKEASKAWGRSSTPVFSFWLYNEKPIDGYLTIDFGEKLISTSEAQAGFKVKLDFTGWRAVGVSLNNDLENREMTLNATNTSSDGTQDSIG RSLGAKVDSIRFKAPSNVSQGEIYIDRIMFSVDDARYQWSDYQVKTRLSEPEIQFHNVKPQLPVTPENLAAIDLIRQRLINEFVGGEKETNLAL EENISKLKSDFDALNIHTLANGGTQGRHLITDKQIIIYQPENLNSQDKQLFDNYVILGNYTTLMFNISRAYVLEKDPTQKAQLKQMYLLMTKHL LDQGFVKGSALVTTHHWGYSSRWWYISTLLMSDALKEANLQTQVYDSLLWYSREFKSSFDMKVSADSSDLDYFNTLSRQHLALLLLEPDDQKRI NLVNTFSHYITGALTQVPPGGKDGLRPDGTAWRHEGNYPGYSFPAFKNASQLIYLLRDTPFSVGESGWNNLKKAMVSAWIYSNPEVGLPLAGRH PFNSPSLKSVAQGYYWLAMSAKSSPDKTLASIYLAISDKTQNESTAIFGETITPASLPQGFYAFNGGAFGIHRWQDKMVTLKAYNTNVWSSEIY NKDNRYGRYQSHGVAQIVSNGSQLSQGYQQEGWDWNRMQGATTIHLPLKDLDSPKPHTLMQRGERGFSGTSSLEGQYGMMAFDLIYPANLERFD PNFTAKKSVLAADNHLIFIGSNINSSDKNKNVETTLFQHAITPTLNTLWINGQKIENMPYQTTLQQGDWLIDSNGNGYLITQAEKVNVSRQHQV SAENKNRQPTEGNFSSAWIDHSTRPKDASYEYMVFLDATPEKMGEMAQKFRENNGLYQVLRKDKDVHIILDKLSNVTGYAFYQPASIEDKWIKK VNKPAIVMTHRQKDTLIVSAVTPDLNMTRQKAATPVTINVTINGKWQSADKNSEVKYQVSGDNTELTFTSYFGIPQEIKLSPLPDYKDDDDK >SEQ_ID_NO:_4_chondroitin_ABC_lyase_DNA atgaagaaaaagattatttcagcaattttgatgtctacagttatcttatcagcagctgctccactttcaggagtttatgcagcaacttctaatc ctgcgtttgacccaaaaaatttaatgcaatcagaaatttaccattttgcacaaaataacccattagcagatttctcttctgataaaaattcaat tttgactctttcagataaacgctctattatgggcaaccaaagtcttctctggaaatggaaaggtggtagctcattcactttacataaaaaactt atcgttccaacagataaagaagcttcaaaggcgtggggtcgcagttctacaccggtgttttctttttggctctataatgaaaaaccaatcgacg gataccttactattgatttcggtgaaaagcttatctcaacttcagaagctcaagccggtttcaaggtcaaattggatttcactggatggcgcgc agtaggtgttagtctcaataatgacttagaaaaccgtgaaatgacacttaatgctactaatacttcaagtgatggaacacaagactcaatcggt cgttctttgggtgctaaagttgactcaattcgtttcaaagcgccatcaaatgtttcacaaggcgaaatctatattgaccgcatcatgttctctg ttgacgatgctcgttaccaatggtcagattaccaagttaaaactcgtctttcagaaccagaaattcaatttcacaatgttaaaccacaacttcc agttactcctgaaaatttggcagcaatcgatttgattagacaacgtcttatcaatgaattcgtaggtggagaaaaagaaacaaatcttgcattg gaagaaaatatctctaaacttaaatcagatttcgatgctttgaatatccatactttggcaaatggaggaactcaaggccgtcacttgatcactg ataaacaaattatcatttatcaaccagaaaacttgaattctcaagacaaacaattgtttgacaactacgttattttgggcaattacacaacatt aatgtttaatatttcacgtgcttatgtccttgaaaaagaccctacacaaaaagctcaactcaaacaaatgtacttgcttatgacaaaacacttacttgatcaaggtttcgttaaaggttcagcgttggtcacaacacatcattggggttattcatcacgttggtggtatatctcaactttattgatgagtgatgcactaaaagaagctaaccttcaaactcaagtttatgattctttgttgtggtacagtcgtgaatttaaatcatcattcgatatgaaagt tagcgcagattcttcagacctcgattactttaacacactttcacgtcaacacctcgctcttttgcttcttgaaccagatgaccaaaaacgtatt aaccttgtgaacactttcagtcactatatcacaggtgcattaacacaagtaccaccaggaggtaaagatggattacgtccagacggtactgctt ggcgtcatgaaggtaactacccaggttactcatttcctgcctttaaaaatgcaagtcaacttatctatcttcttcgtgatacaccatttagcgt tggtgaatcaggttggaataatttgaaaaaagcaatggtttcagcttggatttattcaaatccagaagtaggtcttcctcttgccggtcgtcat ccttttaattcaccttcacttaaatctgttgctcaaggttactattggttggccatgtcagctaaatcatcacctgataaaacacttgcaagca tttaccttgcaatttctgataaaactcaaaatgaatcaactgctattttcggagaaactatcactccagcttcacttccacaaggtttttatgc ctttaatggcggtgcctttggtatccaccgttggcaagacaaaatggttactcttaaagcttacaatactaacgtgtggtcttcagaaatttac aacaaagacaatcgttatggacgttatcaatcacacggtgttgcgcaaattgtctcaaacggttctcaattgtctcaaggttatcaacaagaag gatgggattggaaccgtatgcaaggagccactacaatccaccttccattgaaagaccttgactcaccaaaaccacacacattaatgcaacgtgg agaacgtggtttttctgggacttcttcacttgaaggtcaatacggtatgatggcatttgacttgatctatccggcaaacttagaacgttttgat ccaaactttacagctaaaaaatctgttttggcggccgataaccaccttatcttcatcggcagcaacatcaactcatctgacaaaaataaaaacg ttgaaactactttgttccaacatgcaattactcctactcttaatactctttggattaatggtcaaaaaattgaaaatatgccatatcaaactac tctacaacaaggtgattggcttatcgattcgaatggaaacggttacttgatcactcaagctgaaaaagtcaacgtttctcgtcaacaccaagtaagtgctgaaaataaaaaccgtcaaccaactgaaggtaatttttcatcagcatggatcgaccacagcacacgtcctaaagatgcatcttatgaatatatggtatttttggatgcgactcctgaaaaaatgggtgaaatggcacaaaaattccgtgaaaacaacggtctttatcaagttcttcgtaaaga taaagacgttcacattattttagataagctttcaaacgttacaggttacgccttttaccaaccagcatcaatcgaagataaatggattaaaaaa gtaaataaaccagctattgttatgactcatcgtcaaaaagatactcttatcgtttcagctgttactcctgatcttaatatgactcgtcaaaaag ctgcgactccagttactattaacgtcactattaatggcaaatggcaatctgcagataaaaattcagaagttaaatatcaagtttctggtgacaa cactgaacttacattcacatcatatttcggtattccacaagaaataaaactatctccattaccagattacaaagacgacgacgacaaataa >SEQ_ID_NO:_5_Arcanobacterium_Neuraminidase_AA MKGAKMPPLKSMRKRFTRVFAGASAVALLSLGMVPAVAGAAPSTAEPPASGTATTAAPTTNSPVTASSFKILNPKAEGESFEEGEEIRFQVTLK NDTDVQRAFAFQSSNLNDYQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSFTPRVTWIMRESTGHASPVEKTGEAVGKPVPVTTKLAKLSPI TVTSGEGKASYSAGDQFGYDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSAKYAVTEEDLERGEAELTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKTPNADPNLGARLTDLNILDEKTSEYNIRIPAIAVASNGDILASYDLRPLNGAWHGGDSPNENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFGWSDPSYVVDHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDTHRQTMNFALSSSTDNGRTWNSRLITNDVLSTSGTHIDEIKG CFATSGAGIQKMHEPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFTSDTEGAPAGKHWNFDENKIAELSDGRLMLNSRIPGNSYGTG YRLVAYSADGGETWGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSNTEKPNNRVDGKVKMSYDDGKSWPIAKQIRNGHTGYTTMAVQ PDGSIGLLMEPTSQSVGYVNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPIKVTSTGNDPALADTYSAEGLPAGLKINAETGQIEGTPAVGN TDVKSFDVKVTLTEAEDGTGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEPTPKPEPKPEPTPKPEPKPTPKPEPKVEVVVPNAPVFPDASD PVTCTVKPFVTLQPTKGVSYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKAVEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKP TPDPKPTPEPKPTPDPKPTIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGGAIAIIRRRQG >SEQ_ID_NO:_6_Arcanobacterium_Neuraminidase_DNA atgaaaggtgcaaagatgcccccattgaaatcgatgcgaaaacgattcacgcgagttttcgccggcgctagtgctgtagcgttgttaagtcttg gtatggttccggcggttgcaggtgcagccccgagcacagcggaaccgcctgcttcgggaacagccacaacagcggctcccactacgaattcgcc cgttacagcttcgagcttcaagattctcaaccccaaagccgagggcgaaagttttgaagagggcgaggagatcagattccaggtcaccctcaag aacgacactgatgttcagcgcgcatttgccttccagagctccaacctcaacgattatcaaaaatgtaaatggtggaaagtcgaaccgggtgaga ctaaggaagattgcaaatttcctcaccataaagtcacagctgatgatgtagccacagggtccttcacgcctcgagtcacatggatcatgcgcga atcaacagggcatgcttctccggttgaaaagacaggtgaagccgttggcaaaccggttccagtgaccaccaagctcgcaaagctttcgcctatc accgtgaccagcggagaaggtaaggcatcctacagtgccggggatcagtttggttacgattacaccgtcacctcgctatcaaaagataagattt ccgtcgagggtgaaggatgtccggctaaggagctcgatccggaaaagagcatgaagtgctcggcaaagtacgcggtcacggaggaagacctgga gcgaggcgaagccgaattaactgccaaggttaaagtcagtgacgggaagcgaaacgtcactctcacagaaacaaagtcagtcaaaactcctcgg gtatggccgcaggcaaaggcttttaagacgccgaacgccgatccgaacctgggtgcccggctcaccgacctcaacattctcgatgagaagacta gcgaatacaacattcgtattcccgccatcgcggttgcctccaatggtgacatcctggcttcctatgacctccgtccgctcaacggcgcgtggca cggcggcgattctccgaatgagaattccattgtccaacgccggtcgactgacggcggcaagacctggggtccgagaaccactgtcgccgagggc aaggtcgcaggacagggaaagcgtttcggctggtccgacccctcctacgtcgttgaccacacgactggcgagatcttcaacttccacgtcggtt ctcttgacgcaggtttgcctaataatccttcctaccgtctcgtaaacggaaaagtggacgatactcaccgccagacgatgaatttcgcgttatc gtcatccacagacaacggccgcacctggaattcacgtctgattacgaatgatgtactcagtaccagtggtacccacatagatgaaattaaaggt tgcttcgcaacgtcgggcgccggcattcagaagatgcacgagcctttcaaaggccgtctcctccagcaagcagcatgcaagttcaatactggtc gcttccgcgccatcaccatcttctcagatgaccatggcaagacctggcagggtggccatttcacttcggacactgagggtgctcccgcaggcaa gcactggaacttcgatgagaacaagatcgccgaactgtccgatggtcgcctcatgctgaactcccgtatcccaggcaactcatacggaacgggt taccgtctggtagcttattctgctgatggaggcgaaacctggggcggttatcatatcgaaaagcagcttcctgattccacaaataatgcacagc tcatccgcgccttcccgtcggcaaacaacggcacgctgcgcgcgaaggtactcctcttctctaacacggagaaaccaaacaatcgcgtcgatgg taaagtcaagatgagctacgatgacggcaagtcttggcctatcgccaagcagattcgcaacggccatactggttacaccacgatggcggttcag cccgacggttcgatcggcctgctcatggagccgactagccaaagcgttggctacgtgaacttcacgctcaagacgctcgctgagaatctgcctt tcgaagtcgctcttgacaagattggcgatgtcaaggccaccgacggaacgccgatagcacccatcaaggtgacctccaccggcaatgatccagc cctcgcggacacctactcagctgaaggactcccggctgggttgaagatcaatgccgaaactggccagattgaaggcacccctgcggttggcaac acggacgtgaagagctttgacgtcaaggtgaccttgaccgaggctgaggacggcacgggtatcccgcgcacgtcgtcgcagaccttcaagatca cccttgccccgaacccgacgccggcaccagctcccgagccgaagccggaaccaaagcccgagcctactccgaagccggaaccaaagcccgagcc tactccgaagccggaaccgaagccgacaccgaagccagagccgaaggttgaagttgttgttccgaatgctccggtcttcccggatgcgtctgat ccggttacatgcacggttaagccgtttgtcacgctccagccgacaaagggtgtatcgtactcggtaacagttgatggcaaggagcttgactggg ttgagggcaatccgtcgaggttcgaatacgactatggcaagaccgttgtggtcaaggccaaggctgtcgagggcttcgagttggctaagggtgc aaagacgcagtggtcgtggactgccccgacactcgacgagctcgggtgcacaacgcccgcacccgatcccaagcccacgccggatcccaagccc acgcccgatcccaagcccacgcctgagcccaagccgacgccggatcccaagccgacaataatcgcccaggctaaggcgccgaagtctagcctgg tccacaccggtgctacggtcgttggcctgtcggtcgctgccgcggttctgctcctcgcaggtggtgctatcgcgattattcgccgtcgtcaggg ctaa >SEQ_ID_NO:_7_PNGase_AA MRKLLIFSISAYLMAGIVSCKGVDSATPVTEDGLALNAVNAPADNTVNIKTFDKVKNAFGDGLSQSAEGTFTFPADVTTVKTIKMFIKNECPNK TCDEWDRYANVYVKNKTTGEWYEIGRFITPYWVGTEKLPRGLEIDVTDFKSLLSGNTELKIYTETWLAKGREYSVDFDIVYGTPDYKYSAVVPV IQYNKSSIDGVPYGKAHTLGLKKNIQLPTNTEKAYLRTTISGWGHAKPYDAGSRGCAEWCFRTHTIAINNANTFQHQLGALGCSANPINNQSPG IWAPDRAGWCPGMAVPTRIDVLNNSLTGSTFSYEYKFQSWTNNGTNGDAFYAISSFVIAKSNTPISAPVVTN>SEQ_ID_NO:_8_PNGase_DNAatgagaaaactactaatttttagtatatctgcttacttgatggcaggtatcgtttcgtgtaaaggtgtagacagtgcaacacctgtaacagaag atggcttagctctgaatgcggtaaatgctccggcagataataccgtaaatattaaaacattcgacaaagtaaaaaatgcctttggtgacggatt gtcccaaagtgcagaaggaacctttacatttccggccgatgtaacaactgtaaaaacgattaagatgttcatcaaaaatgaatgtcctaataaa acctgtgatgaatgggatcgttatgccaatgtttatgtaaaaaataaaacaacaggagaatggtatgaaataggacgctttattactccatatt gggtgggtacggaaaaattacctcgtggactggaaattgatgttaccgatttcaaatctttactgtcgggaaatacagaacttaaaatttatac ggagacttggttggccaaaggaagagaatacagtgtagactttgatattgtatatggtacaccggattataaatattcggcagtagtacctgta atccaatataacaaatcatccattgatggtgttccttatggtaaagcacatacactgggattaaaaaagaatattcagttaccaacaaacacgg aaaaagcttatcttagaactactatttccggatggggacatgccaagccatatgatgcgggaagcaggggctgtgcagaatggtgcttcagaac acatactatagcaataaataatgcgaatactttccaacaccagctgggtgctttaggatgttcagcaaaccctattaataatcagagtccggga atttgggctcctgacagagcagggtggtgtccgggaatggcagtgccaacacgtatagatgtgttgaataactctttaacgggtagtactttta gttatgaatataagttccagagttggacaaacaacggaaccaatggagatgctttttatgcaatttccagttttgtgattgcaaaaagtaatac acctattagtgctccggtagttacaaactaa >SEQ_ID_NO:_9_E_coli_pflECTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCaaccatcctcaaaatgtactttttgtctgaatgtagactatcacgggaaaactctctgaacaGTTGACGCACATCAAtcTAACTTtcattcgaaagTATTTTaatgcttgaacgaaaAGCTGTCACC GGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGCCTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_10_Salmonella_pflE CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCccactttacggataaacataccaaagcacggtt tatggccgtgctgtatcaacagataattactgtcatcagacgcaaagccagcttacccaagctccgactgacgatcggctcaagcagcgcggca tcatcttaaacgccataccacaacctcaaaccgtgatgttgtacctcatttaacgcctctttgtcagaacctctccattcgttgacgcacatca agatagctttcattcgaaagtaatttaatctttatatgaaaAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGC CTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_11_E_coli_pepTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCgtaaacgcaacggatggcttaccgatgcggggtttgtggttaaccaccttggtgactcttaatgagggcggtaattctacggcaaaccgcttgaatcgccaatctttgttgtgaattactggcttag ctttatattcattaaggtaatgctgataaatattcccgcttgcaggggtaaaagtgacctgacgcaatatttgtcttttcttgcttcttaataa tgttgtcacaaaaagAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGCCTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_12_Vitreoscilla_pvhb CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCtgtggattaagttttaagaggcaataaagatta taataagtgctgctacaccatactgatgtatggcaaaaccataataatgaacttAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTG AGGACGAAACAGCCTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_13_stm1787 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCgccctctttcaaacagtctcttttttgcattcc tttaaaaccagcatcactattttatataaaaatcatcacgaagtatgcttcttttaacgatgacctcaaatcctccccccttttgcatcaactt acgcatccctgaaatggcgagaacaggctaaatctacccgaggtcactcgctaaaaacctcatcctggaacaagctcaaccgcccttccccgct acggccctttcgccgaaaaaccgataatgggtataaatataccgctataagctatacccacacacttcacattgtttcttatcgttaatccgat acgcttttttcacattatttctggcggtatacgccggtgcaaagtgaatcgggctcgtttccgcgctcgcgcgtaacacaatgatttaccttgc tggcggaacgtcaacggacccgcaaaagcgccttatgcccctggcggagcgtggtAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGT GAGGACGAAACAGCCTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_14_hyaA_MG1655 Tgagtcactctctatgacagatgtaattaattaagcagcataatgataatgcgtaagggcacccagaagttttacccatctttacgcatttgat ctggaacaggtttaacagcggattatcaggtcattaagcaaatataacgccctgagaatttcgacaggcaaaagaaaaaggggttagcatttag ctaaccccttatcttatttggcggaagcgcagagattcgaactctggaaccctttcgggtcgccggttttcaagaccggtgccttcaaccgctc ggccacacttccggaatgacgcgcactataaacatcccgatgcggcgtgtaaacccctaatttgtttgtttgcctgaaaaacagccaaaagtgc attgatagcgtgaaataacagcagattgatcatttcatcaccatgaattccttctcttttactcgtttagcaaccggctaaacatccccaccgc ccggccaaaagaaaaataggtccatttttatcgctaaaagataaatccacacagtttgtattgttttgtgcaaaagtttcactacgctttatta acaatactttctggcgacgtgcgccagtgcagaaggatgagctttcgttttcagcatctcacgtgaagcgatggtttgccttgctacagggacg tcgcttgccgaccataagcgcccggtgtcctgccggtgtcgcaaggaggagagacgtgcgat >SEQ_ID_NO:_15_P2 tacagatctggaagtaattctagagctttgcatgtctataaaaaaatgggattccaaattaccgatatcaatatgcgaaaagaactatgaatat ccactccatttttggttgccatttgttaacgctgcctcctctccctagtgctataataaaaatggcccattttggaacagacttctactatttt gttgtctagtaggagctc >SEQ_ID_NO:_16_P1 tacagatctggaagtaattctagagctttgcatgtctataaaaaaatgggattccaaattaccgatatcaatatgcgaaaagaactatgaatat ccactccatttttggttgccatttgttaacgctgcctcctctccctagtgctataataaaaatggcccattttggaacgagctc >SEQ_ID_NO:_17_PelB_AA MKYLLPTAAAGLLLLAAQPAMA >SEQ_ID_NO:_18_PelB_DNA Atgaaatacctgctgccgaccgctgctgctggtctgctgctcctcgctgcccagccggccatggcc >SEQ_ID_NO:_19_YebF_AA MKKRGAFLGLLLVSACASVFAANNETSKSVTFPKCEDLDAAGIAASVKRDYQQNRVARWADDQKIVGQADPVAWVSLQDIQGKDDKWSVPLTVR GKSADIHYQVSVDCKAGMAEYQRR >SEQ_ID_NO:_20_YebF_DNA atgaaaaaaagaggggcgtttttagggctgttgttggtttctgcctgcgcatcagttttcgctgccaataatgaaaccagcaagtcggtcactttcccaaagtgtgaagatctggatgctgccggaattgccgcgagcgtaaaacgtgattatcaacaaaatcgcgtggcgcgttgggcagatgatcaaaaaattgtcggtcaggccgatcccgtggcttgggtcagtttgcaggacattcagggtaaagatgataaatggtcagtaccgctaaccgtgcgt ggtaaaagtgccgatattcattaccaggtcagcgtggactgcaaagcgggaatggcggaatatcagcggcgt >SEQ_ID_NO:_21_YebF_MMP_AA MKKRGAFLGLLLVSACASVFAANNETSKSVTFPKCEDLDAAGIAASVKRDYQQNRVARWADDQKIVGQADPVAWVSLQDIQGKDDKWSVPLTVR GKSADIHYQVSVDCKAGMAEYQRRPLGLWA >SEQ_ID_NO:_22_YebF_MMP_DNA Atgaaaaaaagaggggcgtttttagggctgttgttggtttctgcctgcgcatcagttttcgctgccaataatgaaaccagcaagtcggtcactt tcccaaagtgtgaagatctggatgctgccggaattgccgcgagcgtaaaacgtgattatcaacaaaatcgcgtggcgcgttgggcagatgatca aaaaattgtcggtcaggccgatcccgtggcttgggtcagtttgcaggacattcagggtaaagatgataaatggtcagtaccgctaaccgtgcgt ggtaaaagtgccgatattcattaccaggtcagcgtggactgcaaagcgggaatggcggaatatcagcggcgtCCATTAGGATTATGGGCA >SEQ_ID_NO:_23_CtxB_AAMIKLKFGVFFTVLLSSAYANGTPQNITDL>SEQ_ID_NO:_24_CtxB_DNA Atgattaaattaaaatttggtgttttttttacagttttactatcttcagcatatgcaaatggaacacctcaaaatattactgatttg >SEQ_ID_NO:_25_AIDA_AA LNPTKESAGNTLTVSNYTGTPGSVISLGGVLEGDNSLTDRLVVKGNTSGQSDIVYVNEDGSGGQTRDGINIISVEGNSDAEFSLKNRVVAGAYD YTLQKGNESGTDNKGWYLTSHLPTSDTRQYRPENGSYATNMALANSLFLMDLNERKQFRAMSDNTQPESASVWMKITGGISSGKLNDGQNKTTT NQFINQLGGDIYKFHAEQLGDFTLGIMGGYANAKGKTINYTSNKAARNTLDGYSVGVYGTWYQNGENATGLFAETWMQYNWFNASVKGDGLEEE KYNLNGLTASAGGGYNLNVHTWTSPEGITGEFWLQPHLQAVWMGVTPDTHQEDNGTVVQGAGKNNIQTKAGIRASWKVKSTLDKDTGRRFRPYI EANWIHNTHEFGVKMSDDSQLLSGSRNQGEIKTGIEGVITQNLSVNGGVAYQAGGHGSNAISGALGIKYSF>SEQ_ID_NO:_26_AIDA_DNActtaatcctacaaaagaaagtgcaggtaatactcttaccgtgtcaaattatactgggacaccgggaagtgttatttctcttggtggtgtgcttg aaggagataattcacttacggaccgtctggtggtgaaaggtaatacctctggtcaaagtgacatcgtttatgtcaatgaagatggcagtggtgg tcagacgagagatggtattaatattatttctgtagagggaaattctgatgcagaattctctctgaagaaccgcgtagttgccggagcttatgat tacacactgcagaaaggaaacgagagtgggacagataataagggatggtatttaaccagtcatcttcccacatctgatacccggcaatacagac cggagaacggaagttatgctaccaatatggcactggctaactcactgttcctcatggatttgaatgagcgtaagcaattcagggccatgagtga taatacacagcctgagtctgcatccgtgtggatgaagatcactggaggaataagctctggtaagcttaatgacgggcaaaataaaacaacaacc aatcagtttatcaatcagctcgggggggatatttataaattccatgctgaacaactgggtgattttaccttagggattatgggaggatacgcga atgcaaaaggtaaaacgataaattacacgagcaacaaagctgccagaaacacactggatggttattctgtcggggtatacggtacgtggtatca gaatggggaaaatgcaacagggctctttgctgaaacttggatgcaatataactggtttaatgcatcagtgaaaggtgacggactggaagaagaa aaatataatctgaatggtttaaccgcttctgcaggtgggggatataacctgaatgtgcacacatggacatcacctgaaggaataacaggtgaat tctggttacagcctcatttgcaggctgtctggatgggggttacaccggatacacatcaggaggataacggaacggtggtgcagggagcagggaa aaataatattcagacaaaagcaggtattcgtgcatcctggaaggtgaaaagcaccctggataaggataccgggcggaggttccgtccgtatata gaggcaaactggatccataacactcatgaatttggtgttaaaatgagtgatgacagccagttgttgtcaggtagccgaaatcagggagagataa agacaggtattgaaggggtgattactcaaaacttgtcagtgaatggcggagtcgcatatcaggcaggaggtcacgggagcaatgccatctccgg agcactggggataaaatacagcttctga >SEQ_ID_NO:_27_MMP-AIDA_AA PLGLWALNPTKESAGNTLTVSNYTGTPGSVISLGGVLEGDNSLTDRLVVKGNTSGQSDIVYVNEDGSGGQTRDGINIISVEGNSDAEFSLKNRV VAGAYDYTLQKGNESGTDNKGWYLTSHLPTSDTRQYRPENGSYATNMALANSLFLMDLNERKQFRAMSDNTQPESASVWMKITGGISSGKLNDG QNKTTTNQFINQLGGDIYKFHAEQLGDFTLGIMGGYANAKGKTINYTSNKAARNTLDGYSVGVYGTWYQNGENATGLFAETWMQYNWFNASVKG DGLEEEKYNLNGLTASAGGGYNLNVHTWTSPEGITGEFWLQPHLQAVWMGVTPDTHQEDNGTVVQGAGKNNIQTKAGIRASWKVKSTLDKDTGR RFRPYIEANWIHNTHEFGVKMSDDSQLLSGSRNQGEIKTGIEGVITQNLSVNGGVAYQAGGHGSNAISGALGIKYSF >SEQ_ID_NO:_28_MMP-AIDA_DNA CCATTAGGATTATGGGCActtaatcctacaaaagaaagtgcaggtaatactcttaccgtgtcaaattatactgggacaccgggaagtgttattt ctcttggtggtgtgcttgaaggagataattcacttacggaccgtctggtggtgaaaggtaatacctctggtcaaagtgacatcgtttatgtcaa tgaagatggcagtggtggtcagacgagagatggtattaatattatttctgtagagggaaattctgatgcagaattctctctgaagaaccgcgta gttgccggagcttatgattacacactgcagaaaggaaacgagagtgggacagataataagggatggtatttaaccagtcatcttcccacatctg atacccggcaatacagaccggagaacggaagttatgctaccaatatggcactggctaactcactgttcctcatggatttgaatgagcgtaagca attcagggccatgagtgataatacacagcctgagtctgcatccgtgtggatgaagatcactggaggaataagctctggtaagcttaatgacggg caaaataaaacaacaaccaatcagtttatcaatcagctcgggggggatatttataaattccatgctgaacaactgggtgattttaccttaggga ttatgggaggatacgcgaatgcaaaaggtaaaacgataaattacacgagcaacaaagctgccagaaacacactggatggttattctgtcggggt atacggtacgtggtatcagaatggggaaaatgcaacagggctctttgctgaaacttggatgcaatataactggtttaatgcatcagtgaaaggt gacggactggaagaagaaaaatataatctgaatggtttaaccgcttctgcaggtgggggatataacctgaatgtgcacacatggacatcacctg aaggaataacaggtgaattctggttacagcctcatttgcaggctgtctggatgggggttacaccggatacacatcaggaggataacggaacggt ggtgcagggagcagggaaaaataatattcagacaaaagcaggtattcgtgcatcctggaaggtgaaaagcaccctggataaggataccgggcgg aggttccgtccgtatatagaggcaaactggatccataacactcatgaatttggtgttaaaatgagtgatgacagccagttgttgtcaggtagcc gaaatcagggagagataaagacaggtattgaaggggtgattactcaaaacttgtcagtgaatggcggagtcgcatatcaggcaggaggtcacgg gagcaatgccatctccggagcactggggataaaatacagcttctga >SEQ_ID_NO:_29_FLAG-MMP-AIDA_AA DYKDDDDKPLGLWALNPTKESAGNTLTVSNYTGTPGSVISLGGVLEGDNSLTDRLVVKGNTSGQSDIVYVNEDGSGGQTRDGINIISVEGNSDA EFSLKNRVVAGAYDYTLQKGNESGTDNKGWYLTSHLPTSDTRQYRPENGSYATNMALANSLFLMDLNERKQFRAMSDNTQPESASVWMKITGGI SSGKLNDGQNKTTTNQFINQLGGDIYKFHAEQLGDFTLGIMGGYANAKGKTINYTSNKAARNTLDGYSVGVYGTWYQNGENATGLFAETWMQYN WFNASVKGDGLEEEKYNLNGLTASAGGGYNLNVHTWTSPEGITGEFWLQPHLQAVWMGVTPDTHQEDNGTVVQGAGKNNIQTKAGIRASWKVKS TLDKDTGRRFRPYIEANWIHNTHEFGVKMSDDSQLLSGSRNQGEIKTGIEGVITQNLSVNGGVAYQAGGHGSNAISGALGIKYSF >SEQ_ID_NO:_30_FLAG-MMP-AIDA_DNA GACTACAAAGACGATGACGACAAGCCATTAGGATTATGGGCActtaatcctacaaaagaaagtgcaggtaatactcttaccgtgtcaaattatactgggacaccgggaagtgttatttctcttggtggtgtgcttgaaggagataattcacttacggaccgtctggtggtgaaaggtaatacctctggtcaaagtgacatcgtttatgtcaatgaagatggcagtggtggtcagacgagagatggtattaatattatttctgtagagggaaattctgatgca gaattctctctgaagaaccgcgtagttgccggagcttatgattacacactgcagaaaggaaacgagagtgggacagataataagggatggtatt taaccagtcatcttcccacatctgatacccggcaatacagaccggagaacggaagttatgctaccaatatggcactggctaactcactgttcct catggatttgaatgagcgtaagcaattcagggccatgagtgataatacacagcctgagtctgcatccgtgtggatgaagatcactggaggaata agctctggtaagcttaatgacgggcaaaataaaacaacaaccaatcagtttatcaatcagctcgggggggatatttataaattccatgctgaac aactgggtgattttaccttagggattatgggaggatacgcgaatgcaaaaggtaaaacgataaattacacgagcaacaaagctgccagaaacac actggatggttattctgtcggggtatacggtacgtggtatcagaatggggaaaatgcaacagggctctttgctgaaacttggatgcaatataac tggtttaatgcatcagtgaaaggtgacggactggaagaagaaaaatataatctgaatggtttaaccgcttctgcaggtgggggatataacctga atgtgcacacatggacatcacctgaaggaataacaggtgaattctggttacagcctcatttgcaggctgtctggatgggggttacaccggatac acatcaggaggataacggaacggtggtgcagggagcagggaaaaataatattcagacaaaagcaggtattcgtgcatcctggaaggtgaaaagc accctggataaggataccgggcggaggttccgtccgtatatagaggcaaactggatccataacactcatgaatttggtgttaaaatgagtgatg acagccagttgttgtcaggtagccgaaatcagggagagataaagacaggtattgaaggggtgattactcaaaacttgtcagtgaatggcggagt cgcatatcaggcaggaggtcacgggagcaatgccatctccggagcactggggataaaatacagcttctga>SEQ_ID_NO:_31_FliC_AAMAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAG >SEQ_ID_NO:_32_FliC_DNA atggcacaagtcattaataccaacagcctctcgctgatcactcaaaataatatcaacaagaaccagtctgcgctgtcgagttctatcgagcgtc tgtcttctggcttgcgtattaacagcgcgaaggatgacgcagcgggt >SEQ_ID_NO:_33_FliC-MMP_AA MAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAGPLGLWA >SEQ_ID_NO:_34_FliC-MMP_DNAatggcacaagtcattaataccaacagcctctcgctgatcactcaaaataatatcaacaagaaccagtctgcgctgtcgagttctatcgagcgtctgtcttctggcttgcgtattaacagcgcgaaggatgacgcagcgggtCCATTAGGATTATGGGCA >SEQ_ID_NO:_35_Usp45_AA MKKKIISAILMSTVILSAAAPLSGVYA >SEQ_ID_NO:_36_Usp45_DNA atgaagaaaaagattatttcagcaattttgatgtctacagttatcttatcagcagctgctccactttcaggagtttatgca >SEQ_ID_NO:_37_PelB-bH_AA MKYLLPTAAAGLLLLAAQPAMADTNVQTPDYEKLRNTWLDVNYGYDKYDENNPDMKKKFDATEKEATNLLKEMKTESGRKYLWSGAETLETNSS HMTRTYRNIEKIAEAMRNPKTTLNTDENKKKVKDALEWLHKNAYGKEPDKKVKELSENFTKTTGKNTNLNWWDYEIGTPKSLTNTLILLNDQFS NEEKKKFTAPIKTFAPDSDKILSSVGKAELAKGGNLVDISKVKLLECIIEEDKDMMKKSIDSFNKVFTYVQDSATGKERNGFYKDGSYIDHQDV PYTGAYGVVLLEGISQMMPMIKETPFNDKTQNDTTLKSWIDDGFMPLIYKGEMMDLSRGRAISRENETSHSASATVMKSLLRLSDAMDDSTKAK YKKIVKSSVESDSSYKQNDYLNSYSDIDKMKSLMTDNSISKNGLTQQLKIYNDMDRVTYHNKDLDFAFGLSMTSKNVARYESINGENLKGWHTG AGMSYLYNSDVKHYHDNFWVTADMKRLSGTTTLDNEILKDTDDKKSSKTFVGGTKVDDQHASIGMDFENQDKTLTAKKSYFILNDKIVFLGTGI KSTDSSKNPVTTIENRKANGYTLYTDDKQTTNSDNQENNSVFLESTDTKKNIGYHFLNKPKITVKKESHTGKWKEINKSQKDTQKTDEYYEVTQ KHSNSDNKYGYVLYPGLSKDVFKTKKDEVTVVKQEDDFHVVKDNESVWAGVNYSNSTQTFDINNTKVEVKAKGMFILKKKDDNTYECSFYNPES TNSASDIESKISMTGYSITNKNTSTSNESGVHFELTKDYKDDDDK >SEQ_ID_NO:_38_PelB-bH_DNA atgaaatacctgctgccgaccgctgctgctggtctgctgctcctcgctgcccagccggccatggccgatacgaatgttcaaacgccagattatg aaaaattgaggaacacatggctggacgttaactatggttatgataagtatgatgagaataatccagatatgaagaagaagtttgatgctacaga gaaagaggcgacgaatttactcaaggaaatgaaaactgaaagtggtaggaaatacttgtggtcaggagcggaaacccttgaaactaattcttct catatgactcgtacctatcgtaatattgagaaaatcgcagaagcgatgaggaatcctaaaaccactttaaatactgacgaaaataagaagaaag tgaaagatgcccttgagtggctgcataaaaatgcatatggaaaagaaccagataaaaaagtaaaagaattaagtgagaattttactaaaacaac tggcaagaataccaacttaaattggtgggattatgaaattggaacacctaaatcattaacaaatacgcttatattgctgaatgatcaattttca aatgaagaaaagaaaaaattcactgcccctattaaaactttcgccccagatagtgacaaaatattatcttctgtaggaaaagctgaacttgcta aaggcggaaatctagtagacatttctaaggtgaaacttttagaatgtattatcgaagaagataaagatatgatgaaaaagtctatagattcatt taataaagtcttcacttacgttcaagattctgccactggtaaagaacgtaatggattttataaagatggctcttacattgatcatcaagacgtt ccatacactggtgcttatggcgttgtactcttagaggggatttctcaaatgatgccgatgataaaagaaacaccttttaatgataaaacccaaa atgatacaaccttaaagtcatggattgacgacggatttatgccactcatttataaaggtgaaatgatggatttatcacgaggtagagctatcag tcgtgaaaatgaaaccagtcactcagcatctgcaacagtaatgaaatcattgttgagattaagtgatgccatggatgattcaacaaaagctaag tataaaaagattgtcaaatcttcagtagagtcagattcaagttataaacaaaatgattatttaaattcatattcggacatagataaaatgaagt ctttaatgacagataacagtatttctaaaaacggattaacacaacaacttaaaatatataatgacatggatcgtgtcacctatcataacaaaga cttagactttgcatttggtttaagtatgacgtcgaaaaacgtagcacgctatgaaagtatcaacggagagaatttaaaaggttggcacactggt gctggaatgtcttatttatataacagcgatgtcaaacactatcatgataacttctgggtgacagccgatatgaaacgtttatcaggtacaacaa ctttagacaatgaaatattaaaagatacggatgataaaaagtcgagtaaaacttttgttggcggaacaaaagttgatgaccaacatgctagtat cggaatggattttgaaaatcaggacaaaactttaactgccaaaaaatcatatttcatattaaacgataaaattgtcttcttaggaactggcatt aaaagtactgattcatcaaagaatccagttacaacgattgaaaatcgcaaagcgaatgggtatacgttatatacagacgataaacaaacaacca attctgataatcaggaaaacaattcagtctttttagagtccacagataccaaaaagaacatcggttatcattttttaaacaaaccgaaaataac tgtaaaaaaagaaagtcatactggtaagtggaaagaaataaataaaagtcaaaaggatacacaaaaaactgatgagtattatgaagtaactcaa aagcattctaattctgacaataaatatggatatgtgttgtatccaggcttatctaaagatgtctttaagacaaaaaaagatgaagtaactgtcg ttaagcaagaagatgacttccacgttgtgaaagataatgaatcggtttgggctggtgttaattatagtaatagcactcaaacttttgacattaa caacactaaagtcgaagttaaagccaaaggtatgtttatacttaaaaagaaagatgataacacttatgaatgtagcttctataatcctgaatct acaaattccgcttcagatattgaatctaaaatttcaatgaccggttactctattacaaacaaaaatacgtcgacttctaatgaatccggcgtgc actttgaattaactaaaGACTACAAAGACGATGACGACAAG >SEQ_ID_NO:_39_YebF-bH_AA MKKRGAFLGLLLVSACASVFAANNETSKSVTFPKCEDLDAAGIAASVKRDYQQNRVARWADDQKIVGQADPVAWVSLQDIQGKDDKWSVPLTVRGKSADIHYQVSVDCKAGMAEYQRRPLGLWATYRIKKWQKLSTITLLMAGVITLNGGEFRSVDKHQIAVADTNVQTPDYEKLRNTWLDVNYGYDKYDENNPDMKKKFDATEKEATNLLKEMKTESGRKYLWSGAETLETNSSHMTRTYRNIEKIAEAMRNPKTTLNTDENKKKVKDALEWLHKNAYGKE PDKKVKELSENFTKTTGKNTNLNWWDYEIGTPKSLTNTLILLNDQFSNEEKKKFTAPIKTFAPDSDKILSSVGKAELAKGGNLVDISKVKLLEC IIEEDKDMMKKSIDSFNKVFTYVQDSATGKERNGFYKDGSYIDHQDVPYTGAYGVVLLEGISQMMPMIKETPFNDKTQNDTTLKSWIDDGFMPL IYKGEMMDLSRGRAISRENETSHSASATVMKSLLRLSDAMDDSTKAKYKKIVKSSVESDSSYKQNDYLNSYSDIDKMKSLMTDNSISKNGLTQQ LKIYNDMDRVTYHNKDLDFAFGLSMTSKNVARYESINGENLKGWHTGAGMSYLYNSDVKHYHDNFWVTADMKRLSGTTTLDNEILKDTDDKKSS KTFVGGTKVDDQHASIGMDFENQDKTLTAKKSYFILNDKIVFLGTGIKSTDSSKNPVTTIENRKANGYTLYTDDKQTTNSDNQENNSVFLESTD TKKNIGYHFLNKPKITVKKESHTGKWKEINKSQKDTQKTDEYYEVTQKHSNSDNKYGYVLYPGLSKDVFKTKKDEVTVVKQEDDFHVVKDNESV WAGVNYSNSTQTFDINNTKVEVKAKGMFILKKKDDNTYECSFYNPESTNSASDIESKISMTGYSITNKNTSTSNESGVHFELTKDYKDDDDK >SEQ_ID_NO:_40_YebF-bH_DNA atgaaaaaaagaggggcgtttttagggctgttgttggtttctgcctgcgcatcagttttcgctgccaataatgaaaccagcaagtcggtcactt tcccaaagtgtgaagatctggatgctgccggaattgccgcgagcgtaaaacgtgattatcaacaaaatcgcgtggcgcgttgggcagatgatca aaaaattgtcggtcaggccgatcccgtggcttgggtcagtttgcaggacattcagggtaaagatgataaatggtcagtaccgctaaccgtgcgt ggtaaaagtgccgatattcattaccaggtcagcgtggactgcaaagcgggaatggcggaatatcagcggcgtCCATTAGGATTATGGGCAacatatagaataaagaaatggcaaaaattatccaccattacgttattaatggctggtgtgattactttgaatggtggtgaattcagaagtgttgataaacatcaaatcgctgtggctgatacgaatgttcaaacgccagattatgaaaaattgaggaacacatggctggacgttaactatggttatgataag tatgatgagaataatccagatatgaagaagaagtttgatgctacagagaaagaggcgacgaatttactcaaggaaatgaaaactgaaagtggta ggaaatacttgtggtcaggagcggaaacccttgaaactaattcttctcatatgactcgtacctatcgtaatattgagaaaatcgcagaagcgat gaggaatcctaaaaccactttaaatactgacgaaaataagaagaaagtgaaagatgcccttgagtggctgcataaaaatgcatatggaaaagaa ccagataaaaaagtaaaagaattaagtgagaattttactaaaacaactggcaagaataccaacttaaattggtgggattatgaaattggaacac ctaaatcattaacaaatacgcttatattgctgaatgatcaattttcaaatgaagaaaagaaaaaattcactgcccctattaaaactttcgcccc agatagtgacaaaatattatcttctgtaggaaaagctgaacttgctaaaggcggaaatctagtagacatttctaaggtgaaacttttagaatgt attatcgaagaagataaagatatgatgaaaaagtctatagattcatttaataaagtcttcacttacgttcaagattctgccactggtaaagaac gtaatggattttataaagatggctcttacattgatcatcaagacgttccatacactggtgcttatggcgttgtactcttagaggggatttctca aatgatgccgatgataaaagaaacaccttttaatgataaaacccaaaatgatacaaccttaaagtcatggattgacgacggatttatgccactc atttataaaggtgaaatgatggatttatcacgaggtagagctatcagtcgtgaaaatgaaaccagtcactcagcatctgcaacagtaatgaaatcattgttgagattaagtgatgccatggatgattcaacaaaagctaagtataaaaagattgtcaaatcttcagtagagtcagattcaagttataaacaaaatgattatttaaattcatattcggacatagataaaatgaagtctttaatgacagataacagtatttctaaaaacggattaacacaacaa cttaaaatatataatgacatggatcgtgtcacctatcataacaaagacttagactttgcatttggtttaagtatgacgtcgaaaaacgtagcac gctatgaaagtatcaacggagagaatttaaaaggttggcacactggtgctggaatgtcttatttatataacagcgatgtcaaacactatcatga taacttctgggtgacagccgatatgaaacgtttatcaggtacaacaactttagacaatgaaatattaaaagatacggatgataaaaagtcgagt aaaacttttgttggcggaacaaaagttgatgaccaacatgctagtatcggaatggattttgaaaatcaggacaaaactttaactgccaaaaaat catatttcatattaaacgataaaattgtcttcttaggaactggcattaaaagtactgattcatcaaagaatccagttacaacgattgaaaatcg caaagcgaatgggtatacgttatatacagacgataaacaaacaaccaattctgataatcaggaaaacaattcagtctttttagagtccacagat accaaaaagaacatcggttatcattttttaaacaaaccgaaaataactgtaaaaaaagaaagtcatactggtaagtggaaagaaataaataaaa gtcaaaaggatacacaaaaaactgatgagtattatgaagtaactcaaaagcattctaattctgacaataaatatggatatgtgttgtatccagg cttatctaaagatgtctttaagacaaaaaaagatgaagtaactgtcgttaagcaagaagatgacttccacgttgtgaaagataatgaatcggtt tgggctggtgttaattatagtaatagcactcaaacttttgacattaacaacactaaagtcgaagttaaagccaaaggtatgtttatacttaaaa agaaagatgataacacttatgaatgtagcttctataatcctgaatctacaaattccgcttcagatattgaatctaaaatttcaatgaccggtta ctctattacaaacaaaaatacgtcgacttctaatgaatccggcgtgcactttgaattaactaaaGACTACAAAGACGATGACGACAAG >SEQ_ID_NO:_41_AIDA-bH_AA MIKLKFGVFFTVLLSSAYANGTPQNITDLDTNVQTPDYEKLRNTWLDVNYGYDKYDENNPDMKKKFDATEKEATNLLKEMKTESGRKYLWSGAE TLETNSSHMTRTYRNIEKIAEAMRNPKTTLNTDENKKKVKDALEWLHKNAYGKEPDKKVKELSENFTKTTGKNTNLNWWDYEIGTPKSLTNTLI LLNDQFSNEEKKKFTAPIKTFAPDSDKILSSVGKAELAKGGNLVDISKVKLLECIIEEDKDMMKKSIDSFNKVFTYVQDSATGKERNGFYKDGS YIDHQDVPYTGAYGVVLLEGISQMMPMIKETPFNDKTQNDTTLKSWIDDGFMPLIYKGEMMDLSRGRAISRENETSHSASATVMKSLLRLSDAM DDSTKAKYKKIVKSSVESDSSYKQNDYLNSYSDIDKMKSLMTDNSISKNGLTQQLKIYNDMDRVTYHNKDLDFAFGLSMTSKNVARYESINGEN LKGWHTGAGMSYLYNSDVKHYHDNFWVTADMKRLSGTTTLDNEILKDTDDKKSSKTFVGGTKVDDQHASIGMDFENQDKTLTAKKSYFILNDKI VFLGTGIKSTDSSKNPVTTIENRKANGYTLYTDDKQTTNSDNQENNSVFLESTDTKKNIGYHFLNKPKITVKKESHTGKWKEINKSQKDTQKTD EYYEVTQKHSNSDNKYGYVLYPGLSKDVFKTKKDEVTVVKQEDDFHVVKDNESVWAGVNYSNSTQTFDINNTKVEVKAKGMFILKKKDDNTYEC SFYNPESTNSASDIESKISMTGYSITNKNTSTSNESGVHFELTKDYKDDDDKPLGLWALNPTKESAGNTLTVSNYTGTPGSVISLGGVLEGDNS LTDRLVVKGNTSGQSDIVYVNEDGSGGQTRDGINIISVEGNSDAEFSLKNRVVAGAYDYTLQKGNESGTDNKGWYLTSHLPTSDTRQYRPENGS YATNMALANSLFLMDLNERKQFRAMSDNTQPESASVWMKITGGISSGKLNDGQNKTTTNQFINQLGGDIYKFHAEQLGDFTLGIMGGYANAKGK TINYTSNKAARNTLDGYSVGVYGTWYQNGENATGLFAETWMQYNWFNASVKGDGLEEEKYNLNGLTASAGGGYNLNVHTWTSPEGITGEFWLQP HLQAVWMGVTPDTHQEDNGTVVQGAGKNNIQTKAGIRASWKVKSTLDKDTGRRFRPYIEANWIHNTHEFGVKMSDDSQLLSGSRNQGEIKTGIE GVITQNLSVNGGVAYQAGGHGSNAISGALGIKYSF >SEQ_ID_NO:_42_AIDA-bH_DNA atgattaaattaaaatttggtgttttttttacagttttactatcttcagcatatgcaaatggaacacctcaaaatattactgatttggatacga atgttcaaacgccagattatgaaaaattgaggaacacatggctggacgttaactatggttatgataagtatgatgagaataatccagatatgaa gaagaagtttgatgctacagagaaagaggcgacgaatttactcaaggaaatgaaaactgaaagtggtaggaaatacttgtggtcaggagcggaa acccttgaaactaattcttctcatatgactcgtacctatcgtaatattgagaaaatcgcagaagcgatgaggaatcctaaaaccactttaaata ctgacgaaaataagaagaaagtgaaagatgcccttgagtggctgcataaaaatgcatatggaaaagaaccagataaaaaagtaaaagaattaag tgagaattttactaaaacaactggcaagaataccaacttaaattggtgggattatgaaattggaacacctaaatcattaacaaatacgcttata ttgctgaatgatcaattttcaaatgaagaaaagaaaaaattcactgcccctattaaaactttcgccccagatagtgacaaaatattatcttctg taggaaaagctgaacttgctaaaggcggaaatctagtagacatttctaaggtgaaacttttagaatgtattatcgaagaagataaagatatgat gaaaaagtctatagattcatttaataaagtcttcacttacgttcaagattctgccactggtaaagaacgtaatggattttataaagatggctct tacattgatcatcaagacgttccatacactggtgcttatggcgttgtactcttagaggggatttctcaaatgatgccgatgataaaagaaacac cttttaatgataaaacccaaaatgatacaaccttaaagtcatggattgacgacggatttatgccactcatttataaaggtgaaatgatggattt atcacgaggtagagctatcagtcgtgaaaatgaaaccagtcactcagcatctgcaacagtaatgaaatcattgttgagattaagtgatgccatg gatgattcaacaaaagctaagtataaaaagattgtcaaatcttcagtagagtcagattcaagttataaacaaaatgattatttaaattcatatt cggacatagataaaatgaagtctttaatgacagataacagtatttctaaaaacggattaacacaacaacttaaaatatataatgacatggatcg tgtcacctatcataacaaagacttagactttgcatttggtttaagtatgacgtcgaaaaacgtagcacgctatgaaagtatcaacggagagaat ttaaaaggttggcacactggtgctggaatgtcttatttatataacagcgatgtcaaacactatcatgataacttctgggtgacagccgatatga aacgtttatcaggtacaacaactttagacaatgaaatattaaaagatacggatgataaaaagtcgagtaaaacttttgttggcggaacaaaagt tgatgaccaacatgctagtatcggaatggattttgaaaatcaggacaaaactttaactgccaaaaaatcatatttcatattaaacgataaaattgtcttcttaggaactggcattaaaagtactgattcatcaaagaatccagttacaacgattgaaaatcgcaaagcgaatgggtatacgttatatacagacgataaacaaacaaccaattctgataatcaggaaaacaattcagtctttttagagtccacagataccaaaaagaacatcggttatcattt tttaaacaaaccgaaaataactgtaaaaaaagaaagtcatactggtaagtggaaagaaataaataaaagtcaaaaggatacacaaaaaactgat gagtattatgaagtaactcaaaagcattctaattctgacaataaatatggatatgtgttgtatccaggcttatctaaagatgtctttaagacaa aaaaagatgaagtaactgtcgttaagcaagaagatgacttccacgttgtgaaagataatgaatcggtttgggctggtgttaattatagtaatag cactcaaacttttgacattaacaacactaaagtcgaagttaaagccaaaggtatgtttatacttaaaaagaaagatgataacacttatgaatgt agcttctataatcctgaatctacaaattccgcttcagatattgaatctaaaatttcaatgaccggttactctattacaaacaaaaatacgtcga cttctaatgaatccggcgtgcactttgaattaactaaaGACTACAAAGACGATGACGACAAGCCATTAGGATTATGGGCActtaatcctacaaa agaaagtgcaggtaatactcttaccgtgtcaaattatactgggacaccgggaagtgttatttctcttggtggtgtgcttgaaggagataattca cttacggaccgtctggtggtgaaaggtaatacctctggtcaaagtgacatcgtttatgtcaatgaagatggcagtggtggtcagacgagagatg gtattaatattatttctgtagagggaaattctgatgcagaattctctctgaagaaccgcgtagttgccggagcttatgattacacactgcagaa aggaaacgagagtgggacagataataagggatggtatttaaccagtcatcttcccacatctgatacccggcaatacagaccggagaacggaagt tatgctaccaatatggcactggctaactcactgttcctcatggatttgaatgagcgtaagcaattcagggccatgagtgataatacacagcctg agtctgcatccgtgtggatgaagatcactggaggaataagctctggtaagcttaatgacgggcaaaataaaacaacaaccaatcagtttatcaa tcagctcgggggggatatttataaattccatgctgaacaactgggtgattttaccttagggattatgggaggatacgcgaatgcaaaaggtaaaacgataaattacacgagcaacaaagctgccagaaacacactggatggttattctgtcggggtatacggtacgtggtatcagaatggggaaaatgcaacagggctctttgctgaaacttggatgcaatataactggtttaatgcatcagtgaaaggtgacggactggaagaagaaaaatataatctgaa tggtttaaccgcttctgcaggtgggggatataacctgaatgtgcacacatggacatcacctgaaggaataacaggtgaattctggttacagcct catttgcaggctgtctggatgggggttacaccggatacacatcaggaggataacggaacggtggtgcagggagcagggaaaaataatattcaga caaaagcaggtattcgtgcatcctggaaggtgaaaagcaccctggataaggataccgggcggaggttccgtccgtatatagaggcaaactggat ccataacactcatgaatttggtgttaaaatgagtgatgacagccagttgttgtcaggtagccgaaatcagggagagataaagacaggtattgaa ggggtgattactcaaaacttgtcagtgaatggcggagtcgcatatcaggcaggaggtcacgggagcaatgccatctccggagcactggggataa aatacagcttc >SEQ_ID_NO:_43_FliC-bH_AA MAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAGPLGLWADTNVQTPDYEKLRNTWLDVNYGYDKYDENNPDMKKKFDATE KEATNLLKEMKTESGRKYLWSGAETLETNSSHMTRTYRNIEKIAEAMRNPKTTLNTDENKKKVKDALEWLHKNAYGKEPDKKVKELSENFTKTTGKNTNLNWWDYEIGTPKSLTNTLILLNDQFSNEEKKKFTAPIKTFAPDSDKILSSVGKAELAKGGNLVDISKVKLLECIIEEDKDMMKKSIDSFNKVFTYVQDSATGKERNGFYKDGSYIDHQDVPYTGAYGVVLLEGISQMMPMIKETPFNDKTQNDTTLKSWIDDGFMPLIYKGEMMDLSRGRAIS RENETSHSASATVMKSLLRLSDAMDDSTKAKYKKIVKSSVESDSSYKQNDYLNSYSDIDKMKSLMTDNSISKNGLTQQLKIYNDMDRVTYHNKD LDFAFGLSMTSKNVARYESINGENLKGWHTGAGMSYLYNSDVKHYHDNFWVTADMKRLSGTTTLDNEILKDTDDKKSSKTFVGGTKVDDQHASI GMDFENQDKTLTAKKSYFILNDKIVFLGTGIKSTDSSKNPVTTIENRKANGYTLYTDDKQTTNSDNQENNSVFLESTDTKKNIGYHFLNKPKIT VKKESHTGKWKEINKSQKDTQKTDEYYEVTQKHSNSDNKYGYVLYPGLSKDVFKTKKDEVTVVKQEDDFHVVKDNESVWAGVNYSNSTQTFDIN NTKVEVKAKGMFILKKKDDNTYECSFYNPESTNSASDIESKISMTGYSITNKNTSTSNESGVHFELTKDYKDDDDK >SEQ_ID_NO:_44_FliC-bH_DNA atggcacaagtcattaataccaacagcctctcgctgatcactcaaaataatatcaacaagaaccagtctgcgctgtcgagttctatcgagcgtc tgtcttctggcttgcgtattaacagcgcgaaggatgacgcagcgggtCCATTAGGATTATGGGCAgatacgaatgttcaaacgccagattatga aaaattgaggaacacatggctggacgttaactatggttatgataagtatgatgagaataatccagatatgaagaagaagtttgatgctacagag aaagaggcgacgaatttactcaaggaaatgaaaactgaaagtggtaggaaatacttgtggtcaggagcggaaacccttgaaactaattcttctc atatgactcgtacctatcgtaatattgagaaaatcgcagaagcgatgaggaatcctaaaaccactttaaatactgacgaaaataagaagaaagt gaaagatgcccttgagtggctgcataaaaatgcatatggaaaagaaccagataaaaaagtaaaagaattaagtgagaattttactaaaacaact ggcaagaataccaacttaaattggtgggattatgaaattggaacacctaaatcattaacaaatacgcttatattgctgaatgatcaattttcaa atgaagaaaagaaaaaattcactgcccctattaaaactttcgccccagatagtgacaaaatattatcttctgtaggaaaagctgaacttgctaa aggcggaaatctagtagacatttctaaggtgaaacttttagaatgtattatcgaagaagataaagatatgatgaaaaagtctatagattcattt aataaagtcttcacttacgttcaagattctgccactggtaaagaacgtaatggattttataaagatggctcttacattgatcatcaagacgttc catacactggtgcttatggcgttgtactcttagaggggatttctcaaatgatgccgatgataaaagaaacaccttttaatgataaaacccaaaa tgatacaaccttaaagtcatggattgacgacggatttatgccactcatttataaaggtgaaatgatggatttatcacgaggtagagctatcagt cgtgaaaatgaaaccagtcactcagcatctgcaacagtaatgaaatcattgttgagattaagtgatgccatggatgattcaacaaaagctaagt ataaaaagattgtcaaatcttcagtagagtcagattcaagttataaacaaaatgattatttaaattcatattcggacatagataaaatgaagtc tttaatgacagataacagtatttctaaaaacggattaacacaacaacttaaaatatataatgacatggatcgtgtcacctatcataacaaagac ttagactttgcatttggtttaagtatgacgtcgaaaaacgtagcacgctatgaaagtatcaacggagagaatttaaaaggttggcacactggtg ctggaatgtcttatttatataacagcgatgtcaaacactatcatgataacttctgggtgacagccgatatgaaacgtttatcaggtacaacaac tttagacaatgaaatattaaaagatacggatgataaaaagtcgagtaaaacttttgttggcggaacaaaagttgatgaccaacatgctagtatc ggaatggattttgaaaatcaggacaaaactttaactgccaaaaaatcatatttcatattaaacgataaaattgtcttcttaggaactggcatta aaagtactgattcatcaaagaatccagttacaacgattgaaaatcgcaaagcgaatgggtatacgttatatacagacgataaacaaacaaccaa ttctgataatcaggaaaacaattcagtctttttagagtccacagataccaaaaagaacatcggttatcattttttaaacaaaccgaaaataact gtaaaaaaagaaagtcatactggtaagtggaaagaaataaataaaagtcaaaaggatacacaaaaaactgatgagtattatgaagtaactcaaa agcattctaattctgacaataaatatggatatgtgttgtatccaggcttatctaaagatgtctttaagacaaaaaaagatgaagtaactgtcgt taagcaagaagatgacttccacgttgtgaaagataatgaatcggtttgggctggtgttaattatagtaatagcactcaaacttttgacattaac aacactaaagtcgaagttaaagccaaaggtatgtttatacttaaaaagaaagatgataacacttatgaatgtagcttctataatcctgaatcta caaattccgcttcagatattgaatctaaaatttcaatgaccggttactctattacaaacaaaaatacgtcgacttctaatgaatccggcgtgca ctttgaattaactaaaGACTACAAAGACGATGACGACAAG >SEQ_ID_NO:_45_Usp45-bH_AA MKKKIISAILMSTVILSAAAPLSGVYAATSNPAFDPKNLMQSEIYHFAQNNPLADFSSDKNSILTLSDKRSIMGNQSLLWKWKGGSSFTLHKKL IVPTDKEASKAWGRSSTPVFSFWLYNEKPIDGYLTIDFGEKLISTSEAQAGFKVKLDFTGWRAVGVSLNNDLENREMTLNATNTSSDGTQDSIG RSLGAKVDSIRFKAPSNVSQGEIYIDRIMFSVDDARYQWSDYQVKTRLSEPEIQFHNVKPQLPVTPENLAAIDLIRQRLINEFVGGEKETNLAL EENISKLKSDFDALNIHTLANGGTQGRHLITDKQIIIYQPENLNSQDKQLFDNYVILGNYTTLMFNISRAYVLEKDPTQKAQLKQMYLLMTKHL LDQGFVKGSALVTTHHWGYSSRWWYISTLLMSDALKEANLQTQVYDSLLWYSREFKSSFDMKVSADSSDLDYFNTLSRQHLALLLLEPDDQKRI NLVNTFSHYITGALTQVPPGGKDGLRPDGTAWRHEGNYPGYSFPAFKNASQLIYLLRDTPFSVGESGWNNLKKAMVSAWIYSNPEVGLPLAGRH PFNSPSLKSVAQGYYWLAMSAKSSPDKTLASIYLAISDKTQNESTAIFGETITPASLPQGFYAFNGGAFGIHRWQDKMVTLKAYNTNVWSSEIY NKDNRYGRYQSHGVAQIVSNGSQLSQGYQQEGWDWNRMQGATTIHLPLKDLDSPKPHTLMQRGERGFSGTSSLEGQYGMMAFDLIYPANLERFD PNFTAKKSVLAADNHLIFIGSNINSSDKNKNVETTLFQHAITPTLNTLWINGQKIENMPYQTTLQQGDWLIDSNGNGYLITQAEKVNVSRQHQV SAENKNRQPTEGNFSSAWIDHSTRPKDASYEYMVFLDATPEKMGEMAQKFRENNGLYQVLRKDKDVHIILDKLSNVTGYAFYQPASIEDKWIKK VNKPAIVMTHRQKDTLIVSAVTPDLNMTRQKAATPVTINVTINGKWQSADKNSEVKYQVSGDNTELTFTSYFGIPQEIKLSPLPDYKDDDDK>SEQ_ID_NO:_46_Usp45-bH_DNAatgaagaaaaagattatttcagcaattttgatgtctacagttatcttatcagcagctgctccactttcaggagtttatgcagcaacttctaatc ctgcgtttgacccaaaaaatttaatgcaatcagaaatttaccattttgcacaaaataacccattagcagatttctcttctgataaaaattcaat tttgactctttcagataaacgctctattatgggcaaccaaagtcttctctggaaatggaaaggtggtagctcattcactttacataaaaaactt atcgttccaacagataaagaagcttcaaaggcgtggggtcgcagttctacaccggtgttttctttttggctctataatgaaaaaccaatcgacg gataccttactattgatttcggtgaaaagcttatctcaacttcagaagctcaagccggtttcaaggtcaaattggatttcactggatggcgcgc agtaggtgttagtctcaataatgacttagaaaaccgtgaaatgacacttaatgctactaatacttcaagtgatggaacacaagactcaatcggt cgttctttgggtgctaaagttgactcaattcgtttcaaagcgccatcaaatgtttcacaaggcgaaatctatattgaccgcatcatgttctctg ttgacgatgctcgttaccaatggtcagattaccaagttaaaactcgtctttcagaaccagaaattcaatttcacaatgttaaaccacaacttcc agttactcctgaaaatttggcagcaatcgatttgattagacaacgtcttatcaatgaattcgtaggtggagaaaaagaaacaaatcttgcattg gaagaaaatatctctaaacttaaatcagatttcgatgctttgaatatccatactttggcaaatggaggaactcaaggccgtcacttgatcactg ataaacaaattatcatttatcaaccagaaaacttgaattctcaagacaaacaattgtttgacaactacgttattttgggcaattacacaacatt aatgtttaatatttcacgtgcttatgtccttgaaaaagaccctacacaaaaagctcaactcaaacaaatgtacttgcttatgacaaaacactta cttgatcaaggtttcgttaaaggttcagcgttggtcacaacacatcattggggttattcatcacgttggtggtatatctcaactttattgatga gtgatgcactaaaagaagctaaccttcaaactcaagtttatgattctttgttgtggtacagtcgtgaatttaaatcatcattcgatatgaaagttagcgcagattcttcagacctcgattactttaacacactttcacgtcaacacctcgctcttttgcttcttgaaccagatgaccaaaaacgtattaaccttgtgaacactttcagtcactatatcacaggtgcattaacacaagtaccaccaggaggtaaagatggattacgtccagacggtactgctt ggcgtcatgaaggtaactacccaggttactcatttcctgcctttaaaaatgcaagtcaacttatctatcttcttcgtgatacaccatttagcgt tggtgaatcaggttggaataatttgaaaaaagcaatggtttcagcttggatttattcaaatccagaagtaggtcttcctcttgccggtcgtcat ccttttaattcaccttcacttaaatctgttgctcaaggttactattggttggccatgtcagctaaatcatcacctgataaaacacttgcaagca tttaccttgcaatttctgataaaactcaaaatgaatcaactgctattttcggagaaactatcactccagcttcacttccacaaggtttttatgc ctttaatggcggtgcctttggtatccaccgttggcaagacaaaatggttactcttaaagcttacaatactaacgtgtggtcttcagaaatttac aacaaagacaatcgttatggacgttatcaatcacacggtgttgcgcaaattgtctcaaacggttctcaattgtctcaaggttatcaacaagaag gatgggattggaaccgtatgcaaggagccactacaatccaccttccattgaaagaccttgactcaccaaaaccacacacattaatgcaacgtgg agaacgtggtttttctgggacttcttcacttgaaggtcaatacggtatgatggcatttgacttgatctatccggcaaacttagaacgttttgat ccaaactttacagctaaaaaatctgttttggcggccgataaccaccttatcttcatcggcagcaacatcaactcatctgacaaaaataaaaacg ttgaaactactttgttccaacatgcaattactcctactcttaatactctttggattaatggtcaaaaaattgaaaatatgccatatcaaactactctacaacaaggtgattggcttatcgattcgaatggaaacggttacttgatcactcaagctgaaaaagtcaacgtttctcgtcaacaccaagtaagtgctgaaaataaaaaccgtcaaccaactgaaggtaatttttcatcagcatggatcgaccacagcacacgtcctaaagatgcatcttatgaat atatggtatttttggatgcgactcctgaaaaaatgggtgaaatggcacaaaaattccgtgaaaacaacggtctttatcaagttcttcgtaaaga taaagacgttcacattattttagataagctttcaaacgttacaggttacgccttttaccaaccagcatcaatcgaagataaatggattaaaaaa gtaaataaaccagctattgttatgactcatcgtcaaaaagatactcttatcgtttcagctgttactcctgatcttaatatgactcgtcaaaaag ctgcgactccagttactattaacgtcactattaatggcaaatggcaatctgcagataaaaattcagaagttaaatatcaagtttctggtgacaa cactgaacttacattcacatcatatttcggtattccacaagaaataaaactatctccattaccagattacaaagacgacgacgacaaa >SEQ_ID_NO:_47_Chondroitin_ABC_lyase_AA MPIFRFTALAMTLGLLSAPYNAMAATSNPAFDPKNLMQSEIYHFAQNNPLADFSSDKNSILTLSDKRSIMGNQSLLWKWKGGSSFTLHKKLIVP TDKEASKAWGRSSTPVFSFWLYNEKPIDGYPTIDFGEKLISTSEAQAGFKVKLDFTGWRAVGVSLNNDLENREMTLNATNTSSDGTQDSIGRSL GAKVDSIRFKAPSNVSQGEIYIDRIMFSVDDARYQWSDYQVKTRLSEPEIQFHNVKPQLPVTPENLAAIDLIRQRLINEFVGGEKETNLALEEN ISKLKSDFDALNIHTLANGGTQGRHLITDKQIIIYQPENLNSQDKQLFDNYVILGNYTTLMFNISRAYVLEKDPTQKAQLKQMYLLVTKHLLDQ GFVKGSALVTTHHWGYSSRWWYISTLLMSDALKEANLQTQVYDSLLWYSREFKSSFDMKVSADSSDLDYFNTLSRQHLALLLLEPDDQKRINLV NTFSHYITGALTQVPPGGKDGLRLMVQHGDMKATIRVTLSQPLKMPLSLFIYYAIHHFQLGESGWNNLKKAMVSAWIYSNPEVGLPLAGRHPFN SPSLKSVAQGYYWLAMSAKSSPDKTLASIYLAISDKTQNESTAIFGETITPASLPQGFYAFNGGAFGIHRWQDKMVTLKAYNTNVWSSEIYNKD NRYGRYQSHGVGQIVSNGSQLSQGYQQEGWDWNRMQGATTIHLPLKDLDSPKPHTLMQRGERGFSGTSSLEGQYGMMAFDLIYPANLERFDPNF TAKKSVLAADNHLIFIGSNINSSDKNKNVETTLFQHAITPTLNTLWINGQKIENMPYQTTLQQGDWLIDSNGNGYLITQAEKVNVSRQHQVSAE NKNRQPTEGNFSSAWIDHRTRPKDASYEYMVFLDATPEKMGEMAQKFRENNGLYQVLRKDKDVHIILDKLSNVTGYAFYQPASIEDKWIKKVNK PAIVMTHRQKDTLIVSAVTPDLNMTRQKAATPVTINVTINGKWQSADKNSEVKYQVSGDNTELTFTSYFGIPQEIKLSPLP >SEQ_ID_NO:_48_Chondroitin_ABC_lyase_DNA atgccgatatttcgttttactgcacttgcaatgacattggggctattatcagcgccttataacgcgatggcagccaccagcaatcctgcatttg atcctaaaaatctgatgcagtcagaaatttaccattttgcacaaaataacccattagcagacttctcatcagataaaaactcaatactaacgtt atctgataaacgtagcattatgggaaaccaatctcttttatggaaatggaaaggtggtagtagctttactttacataaaaaactgattgtcccc accgataaagaagcatctaaagcatggggacgctcatctacccccgttttctcattttggctttacaatgaaaaaccgattgatggttatccta ctatcgatttcggagaaaaactcatttcaaccagtgaggctcaggcaggctttaaagtaaaattagatttcactggctggcgtgctgtgggagt ctctttaaataacgatcttgaaaatcgagagatgaccttaaatgcaaccaatacctcctctgatggtactcaagacagcattgggcgttcttta ggtgctaaagtcgatagtattcgttttaaagcgccttctaatgtgagtcagggtgaaatctatatcgaccgtattatgttttctgtcgatgatg ctcgctaccaatggtctgattatcaagtaaaaactcgcttatcagaacctgaaattcaatttcacaacgtaaagccacaactacctgtaacacc tgaaaatttagcggccattgatcttattcgccaacgtctaattaatgaatttgtcggaggtgaaaaagagacaaacctcgcattagaagagaat atcagcaaattaaaaagtgatttcgatgctcttaatattcacactttagcaaatggtggaacgcaaggcagacatctgatcactgataaacaaa tcattatttatcaaccagagaatcttaactcccaagataaacaactatttgataattatgttattttaggtaattacacgacattaatgtttaa tattagccgtgcttatgtgctggaaaaagatcccacacaaaaggcgcaactaaagcagatgtacttattagtgacaaagcatttattagatcaa ggctttgttaaagggagtgctttagtgacaacccatcactggggatacagttctcgttggtggtatatttccacgttattaatgtctgatgcac taaaagaagcgaacctacaaactcaagtttatgattcattactgtggtattcacgtgagtttaaaagtagttttgatatgaaagtaagtgctga tagctctgatctagattatttcaataccttatctcgccaacatttagccttattattactagagcctgatgatcaaaagcgtatcaacttagtt aatactttcagccattatatcactggcgcattaacgcaagtgccaccgggtggtaaagatggtttacgcctgatggtacagcatggcgacatga aggcaactatccgggttactctttcccagcctttaaaaatgcctctcagcttatttatttattacgcgatacaccatttccagttgggtgaaag tggttggaataacctgaaaaaagcgatggtttcagcgtggatctacagtaatccagaagttggattaccgcttgcaggaagacacccttttaac tcaccttcgttaaaatcagtcgctcaaggctattactggcttgccatgtctgcaaaatcatcgcctgataaaacacttgcatctatttatcttg cgattagtgataaaacacaaaatgaatcaactgctatttttggagaaactattacaccagcgtctttacctcaaggtttctatgcctttaatgg cggtgcttttggtattcatcgttggcaagataaaatggtgacactgaaagcttataacaccaatgtttggtcatctgaaatttataacaaagat aaccgttatggccgttaccaaagtcatggtgtcggtcaaatagtgagtaatggctcgcagctttcacagggctatcagcaagaaggttgggatt ggaatagaatgcaaggggcaaccactattcaccttcctcttaaagacttagacagtcctaaacctcataccttaatgcaacgtggagagcgtgg atttagcggaacatcatcccttgaaggtcaatatggcatgatggcattcgatcttatttatcccgccaatcttgagcgttttgatcctaatttc actgcgaaaaagagtgtattagccgctgataatcacttaatttttattggtagcaatataaatagtagtgataaaaataaaaatgttgaaacga ccttattccaacatgccattactccaacattaaataccctttggattaatggacaaaagatagaaaacatgccttatcaaacaacacttcaaca aggtgattggttaattgatagcaatggcaatggttacttaattactcaagcagaaaaagtaaatgtaagtcgccaacatcaggtttcagcggaa aataaaaatcgccaaccgacagaaggaaactttagctcggcatggatcgatcacaggactcgccccaaagatgccagttatgagtatatggtctttttagatgcgacacctgaaaaaatgggagagatggcacaaaaattccgtgaaaataatgggttatatcaggttcttcgtaaggataaagacgttcatattattctcgataaactcagcaatgtaacgggatatgccttttatcagccagcatcaattgaagacaaatggatcaaaaaggttaataaa cctgcaattgtgatgactcatcgacaaaaagacactcttattgtcagtgcagttacacctgatttaaatatgactcgccaaaaagcagcaactc ctgtcaccatcaatgtcacgattaatggcaaatggcaatctgctgataaaaatagtgaagtgaaatatcaggtttctggtgataacactgaact gacgtttacgagttactttggtattccacaagaaatcaaactctcgccactcccttga >SEQ_ID_NO:_49_GadE_AA MIFLMTKDSFLLQGFWQLKDNHEMIKINSLSEIKKVGNKPFKVIIDTYHNHILDEEAIKFLEKLDAERIIVLAPYHISKLKAKAPIYFVSRKES IKNLLEITYGKHLPHKNSQLCFSHNQFKIMQLILKNKNESNITSTLNISQQTLKIQKFNIMYKLKLRRMSDIVTLGITSYF >SEQ_ID_NO:_50_GadE_DNA Atgatttttctcatgacgaaagattcttttcttttacagggcttttggcagttgaaagataatcacgaaatgataaaaatcaattccctgtcag agatcaaaaaagtaggcaataaacccttcaaggttatcattgatacctatcacaatcatatccttgatgaagaagcgattaaatttctggagaa attagatgccgagagaattattgttttggcaccttatcacatcagtaaactaaaagctaaagcgcctatttattttgttagccgcaaagaaagt atcaaaaatcttcttgagattacttatggtaaacacttgccccataagaattcacaattatgtttttcacataatcagttcaaaattatgcaactgattctgaaaaataaaaatgaaagcaatatcacgtcgacgctcaatatttcgcaacaaacattaaagattcagaaattcaacattatgtacaagctgaaactaagacgtatgagcgacatcgtcaccctgggtatcacatcttatttttag >SEQ_ID_NO:_51_rrnB_T1 / T2 Gcttgattaagtccaaataaaacgaaaggctcagtcgaaagactgggcctttcgttttatctgttgtttgtcggtgaacgctctcctgagtagg acaaatccgccgggagcggatttgaacgttgcgaagcaacggcccggagggtggcgggcaggacgcccgccataaactgccaggcatcaaatta agcagaaggccatcctgacggatggcctttt >SEQ_ID_NO:_52_FNR GTTGACGCACATCAA >SEQ_ID_NO:_53_RiboJAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGCCTCTACAAATAATTTTGTTTAA>SEQ_ID_NO:_54_Promoter LOR7 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCccactttacggataaacataccaaagcacggtt tatggccgtgctgtatcaacagataattactgtcatcagacgcaaagccagcttacccaagctccgactgacgatcggctcaagcagcgcggca tcatcttaaacgccataccacaacctcaaaccgtgatgttgtacctcatttaacgcctctttgtcagaacctctccattcgttgacgcacatca agatagctttcattcgaaagtaatttaatctttatatgaaaAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGC CTCTACAAATAATTTTGTTTAAggctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatctaaggaggtagtcc >SEQ_ID_NO:_55_Promoter LOR9 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCccactttacggataaacataccaaagcacggtt tatggccgtgctgtatcaacagataattactgtcatcagacgcaaagccagcttacccaagctccgactgacgatcggctcaagcagcgcggca tcatcttaaacgccataccacaacctcaaaccgtgatgttgtacctcatttaacgcctctttgtcagaacctctccattcgttgacgcacatca agatagctttcattcgaaagtaatttaatctttatatgaaaAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGC CTCTACAAATAATTTTGTTTAAggctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatctcaggaggtagtcc >SEQ_ID_NO:_56_Promoter LOR1 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCccactttacggataaacataccaaagcacggtt tatggccgtgctgtatcaacagataattactgtcatcagacgcaaagccagcttacccaagctccgactgacgatcggctcaagcagcgcggca tcatcttaaacgccataccacaacctcaaaccgtgatgttgtacctcatttaacgcctctttgtcagaacctctccattcgttgacgcacatca agatagctttcattcgaaagtaatttaatctttatatgaaaAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGC CTCTACAAATAATTTTGTTTAActcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatccaaggaggtagtcc >SEQ_ID_NO:_57_Promoter LPR7 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCgccctctttcaaacagtctcttttttgcattcc tttaaaaccagcatcactattttatataaaaatcatcacgaagtatgcttcttttaacgatgacctcaaatcctccccccttttgcatcaactt acgcatccctgaaatggcgagaacaggctaaatctacccgaggtcactcgctaaaaacctcatcctggaacaagctcaaccgcccttccccgct acggccctttcgccgaaaaaccgataatgggtataaatataccgctataagctatacccacacacttcacattgtttcttatcgttaatccgat acgcttttttcacattatttctggcggtatacgccggtgcaaagtgaatcgggctcgtttccgcgctcgcgcgtaacacaatgatttaccttgc tggcggaacgtcaacggacccgcaaaagcgccttatgcccctggcggagcgtggtAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGT GAGGACGAAACAGCCTCTACAAATAATTTTGTTTAAggctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatctaaggaggtagtcc >SEQ_ID_NO:_58_Promoter LPR1 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCgccctctttcaaacagtctcttttttgcattcc tttaaaaccagcatcactattttatataaaaatcatcacgaagtatgcttcttttaacgatgacctcaaatcctccccccttttgcatcaactt acgcatccctgaaatggcgagaacaggctaaatctacccgaggtcactcgctaaaaacctcatcctggaacaagctcaaccgcccttccccgct acggccctttcgccgaaaaaccgataatgggtataaatataccgctataagctatacccacacacttcacattgtttcttatcgttaatccgat acgcttttttcacattatttctggcggtatacgccggtgcaaagtgaatcgggctcgtttccgcgctcgcgcgtaacacaatgatttaccttgc tggcggaacgtcaacggacccgcaaaagcgccttatgcccctggcggagcgtggtAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGT GAGGACGAAACAGCCTCTACAAATAATTTTGTTTAActcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatccaaggaggtagtcc >SEQ_ID_NO:_59_Promoter LPR9 CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCgccctctttcaaacagtctcttttttgcattcc tttaaaaccagcatcactattttatataaaaatcatcacgaagtatgcttcttttaacgatgacctcaaatcctccccccttttgcatcaactt acgcatccctgaaatggcgagaacaggctaaatctacccgaggtcactcgctaaaaacctcatcctggaacaagctcaaccgcccttccccgct acggccctttcgccgaaaaaccgataatgggtataaatataccgctataagctatacccacacacttcacattgtttcttatcgttaatccgat acgcttttttcacattatttctggcggtatacgccggtgcaaagtgaatcgggctcgtttccgcgctcgcgcgtaacacaatgatttaccttgc tggcggaacgtcaacggacccgcaaaagcgccttatgcccctggcggagcgtggtAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGT GAGGACGAAACAGCCTCTACAAATAATTTTGTTTAAggctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatctcaggaggtagtcc>SEQ_ID_NO:_60_hyaA_stm1787CTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCtgagtcactctctatgacagatgtaattaatta agcagcataatgataatgcgtaagggcacccagaagttttacccatctttacgcatttgatctggaacaggtttaacagcggattatcaggtca ttaagcaaatataacgccctgagaatttcgacaggcaaaagaaaaaggggttagcatttagctaaccccttatcttatttggcggaagcgcaga gattcgaactctggaaccctttcgggtcgccggttttcaagaccggtgccttcaaccgctcggccacacttccggaatgacgcgcactataaac atcccgatgcggcgtgtaaacccctaatttgtttgtttgcctgaaaaacagccaaaagtgcattgatagcgtgaaataacagcagattgatcat ttcatcaccatgaattccttctcttttactcgtttagcaaccggctaaacatccccaccgcccggccaaaagaaaaataggtccatttttatcg ctaaaagataaatccacacagtttgtattgttttgtgcaaaagtttcactacgctttattaacaatactttctggcgacgtgcgccagtgcaga aggatgagctttcgttttcagcatctcacgtgaagcgatggtttgccttgctacagggacgtcgcttgccgaccataagcgcccggtgtcctgc cggtgtcgcAGCTGTCACCGGATGTGCTTTCCGGTCTGATGAGTCCGTGAGGACGAAACAGCCTCTACAAATAATTTTGTTTAA >SEQ_ID_NO:_61_P3 tacagatctggaagtaattctagagctttgcatgtctataaaaaaatgggattccaaattaccgatatcaatatgcgaaaagaactatgaatat ccactccatttttggttgccatttgttaacgctgcctcctctccctagtgctataataaaaatggccaaaaaaaaacgagctc>SEQ_ID_NO:_62_U1-RBS1ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatcacacaggacTAGTCC >SEQ_ID_NO:_63_U1-RBS2 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAaaagaggggaaaTAGTCC >SEQ_ID_NO:_64_U1-RBS3 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAaaagaggagaaaTAGTCC >SEQ_ID_NO:_65_U1-RBS-A01 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAatccaaggaggtagtcc>SEQ_ID_NO:_66_U1-RBS-A02ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCCAGGGAGGTAGTCC >SEQ_ID_NO:_67_U1-RBS-A03 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCCCAGGAGGTAGTCC >SEQ_ID_NO:_68_U1-RBS-A04 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCCCGGGAGGTAGTCC >SEQ_ID_NO:_69_U1-RBS-A05 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCCGAGGAGGTAGTCC >SEQ_ID_NO:_70_U1-RBS-A06 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCCGGGGAGGTAGTCC >SEQ_ID_NO:_71_U1-RBS-A07 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTAAGGAGGTAGTCC >SEQ_ID_NO:_72_U1-RBS-A08 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTAGGGAGGTAGTCC >SEQ_ID_NO:_73_U1-RBS-A09 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTCAGGAGGTAGTCC >SEQ_ID_NO:_74_U1-RBS-A10 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTCGGGAGGTAGTCC >SEQ_ID_NO:_75_U1-RBS-A11 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTGAGGAGGTAGTCC >SEQ_ID_NO:_76_U1-RBS-A12 ctcgttgaacaccgtcTCAGGTAAGTATCAGTTGTAAATCTGGGGAGGTAGTCC >SEQ_ID_NO:_77_U2-RBS1 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAatcacacaggacTAGTCC >SEQ_ID_NO:_78_U2-RBS2 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAaaagaggggaaaTAGTCC >SEQ_ID_NO:_79_U2-RBS3 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAaaagaggagaaaTAGTCC >SEQ_ID_NO:_80_U2-RBS-A01 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAatccaaggaggtagtcc >SEQ_ID_NO:_81_U2-RBS-A02 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCCAGGGAGGTAGTCC >SEQ_ID_NO:_82_U2-RBS-A03 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCCCAGGAGGTAGTCC >SEQ_ID_NO:_83_U2-RBS-A04 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCCCGGGAGGTAGTCC >SEQ_ID_NO:_84_U2-RBS-A05 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCCGAGGAGGTAGTCC >SEQ_ID_NO:_85_U2-RBS-A06 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCCGGGGAGGTAGTCC >SEQ_ID_NO:_86_U2-RBS-A07 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTAAGGAGGTAGTCC >SEQ_ID_NO:_87_U2-RBS-A08 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTAGGGAGGTAGTCC >SEQ_ID_NO:_88_U2-RBS-A09 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTCAGGAGGTAGTCC >SEQ_ID_NO:_89_U2-RBS-A10 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTCGGGAGGTAGTCC >SEQ_ID_NO:_90_U2-RBS-A11 CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTGAGGAGGTAGTCC >SEQ_ID_NO:_91_U2-RBS-A12CTCGTGTTACTATTGGCTGAGATAAGGGTAGCAGAAAATCTGGGGAGGTAGTCC>SEQ_ID_NO:_92_U3-RBS1 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAatcacacaggacTAGTCC >SEQ_ID_NO:_93_U3-RBS2 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAaaagaggggaaaTAGTCC >SEQ_ID_NO:_94_U3-RBS3 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAaaagaggagaaaTAGTCC >SEQ_ID_NO:_95_U3-RBS-A01 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAatccaaggaggtagtcc >SEQ_ID_NO:_96_U3-RBS-A02 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCCAGGGAGGTAGTCC >SEQ_ID_NO:_97_U3-RBS-A03 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCCCAGGAGGTAGTCC >SEQ_ID_NO:_98_U3-RBS-A04 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCCCGGGAGGTAGTCC >SEQ_ID_NO:_99_U3-RBS-A05 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCCGAGGAGGTAGTCC >SEQ_ID_NO:_100_U3-RBS-A06 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCCGGGGAGGTAGTCC >SEQ_ID_NO:_101_U3-RBS-A08 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCTAGGGAGGTAGTCC >SEQ_ID_NO:_102_U3-RBS-A09 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCTCAGGAGGTAGTCC >SEQ_ID_NO:_103_U3-RBS-A10 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCTCGGGAGGTAGTCC >SEQ_ID_NO:_104_U3-RBS-A11 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCTGAGGAGGTAGTCC >SEQ_ID_NO:_105_U3-RBS-A12 CTCGGTATCTCGTGGTCTGACGGTAAAATCTATTGTAATCTGGGGAGGTAGTCC >SEQ_ID_NO:_106_Nuraminidase_PelB_AA MKYLLPTAAAGLLLLAAQPAMAAPSTAEPPASGTATTAAPTTNSPVTASSFKILNPKAEGESFEEGEEIRFQVTLKNDTDVQRAFAFQSSNLND YQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSFTPRVTWIMRESTGHASPVEKTGEAVGKPVPVTTKLAKLSPITVTSGEGKASYSAGDQFG YDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSAKYAVTEEDLERGEAELTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKTPNADPNLG ARLTDLNILDEKTSEYNIRIPAIAVASNGDILASYDLRPLNGAWHGGDSPNENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFGWSDPSYVV DHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDTHRQTMNFALSSSTDNGRTWNSRLITNDVLSTSGTHIDEIKGCFATSGAGIQKMHEPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFTSDTEGAPAGKHWNFDENKIAELSDGRLMLNSRIPGNSYGTGYRLVAYSADGGETWGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSNTEKPNNRVDGKVKMSYDDGKSWPIAKQIRNGHTGYTTMAVQPDGSIGLLMEPTSQSVGY VNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPIKVTSTGNDPALADTYSAEGLPAGLKINAETGQIEGTPAVGNTDVKSFDVKVTLTEAEDG TGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEPTPKPEPKPEPTPKPEPKPTPKPEPKVEVVVPNAPVFPDASDPVTCTVKPFVTLQPTKGV SYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKAVEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKPTPDPKPTPEPKPTPDPKP TIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGGAIAIIRRRQGDYKDDDDK >SEQ_ID_NO:_107_Nuraminidase_PelB_DNA atgaaatacctgctgccgaccgctgctgctggtctgctgctcctcgctgcccagccggccatggccgccccgagcacagcggaaccgcctgctt cgggaacagccacaacagcggctcccactacgaattcgcccgttacagcttcgagcttcaagattctcaaccccaaagccgagggcgaaagttt tgaagagggcgaggagatcagattccaggtcaccctcaagaacgacactgatgttcagcgcgcatttgccttccagagctccaacctcaacgat tatcaaaaatgtaaatggtggaaagtcgaaccgggtgagactaaggaagattgcaaatttcctcaccataaagtcacagctgatgatgtagcca cagggtccttcacgcctcgagtcacatggatcatgcgcgaatcaacagggcatgcttctccggttgaaaagacaggtgaagccgttggcaaacc ggttccagtgaccaccaagctcgcaaagctttcgcctatcaccgtgaccagcggagaaggtaaggcatcctacagtgccggggatcagtttggt tacgattacaccgtcacctcgctatcaaaagataagatttccgtcgagggtgaaggatgtccggctaaggagctcgatccggaaaagagcatgaagtgctcggcaaagtacgcggtcacggaggaagacctggagcgaggcgaagccgaattaactgccaaggttaaagtcagtgacgggaagcgaaacgtcactctcacagaaacaaagtcagtcaaaactcctcgggtatggccgcaggcaaaggcttttaagacgccgaacgccgatccgaacctgggt gcccggctcaccgacctcaacattctcgatgagaagactagcgaatacaacattcgtattcccgccatcgcggttgcctccaatggtgacatcc tagcttcttatgacctccgtccactcaacggagcttggcacggaggagattctccgaatgagaattccattgtccaacgccggtcgactgacgg cggcaagacctggggtccgagaaccactgtcgccgagggcaaggtcgcaggacagggaaagcgtttcggctggtccgacccctcctacgtcgtt gaccacacgactggcgagatcttcaacttccacgtcggttctcttgacgcaggtttgcctaataatccttcctaccgtctcgtaaacggaaaag tggacgatactcaccgccagacgatgaatttcgcgttatcgtcatccacagacaacggccgcacctggaattcacgtctgattacgaatgatgt actcagtaccagtggtacccacatagatgaaattaaaggttgcttcgcaacgtcgggcgccggcattcagaagatgcacgagcctttcaaaggc cgtctcctccagcaagcagcatgcaagttcaatactggtcgcttccgcgccatcaccatcttctcagatgaccatggcaagacctggcagggtg gccatttcacttcggacactgagggtgctcccgcaggcaagcactggaacttcgatgagaacaagatcgccgaactgtccgatggtcgcctcat gctgaactcccgtatcccaggcaactcatacggaacgggttaccgtctggtagcttattctgctgatggaggcgaaacctggggcggttatcat atcgaaaagcagcttcctgattccacaaataatgcacagctcatccgcgccttcccgtcggcaaacaacggcacgctgcgcgcgaaggtactcctcttctctaacacggagaaaccaaacaatcgcgtcgatggtaaagtcaagatgagctacgatgacggcaagtcttggcctatcgccaagcagattcgcaacggccatactggttacaccacgatggcggttcagcccgacggttcgatcggcctgctcatggagccgactagccaaagcgttggctac gtgaacttcacgctcaagacgctcgctgagaatctgcctttcgaagtcgctcttgacaagattggcgatgtcaaggccaccgacggaacgccga tagcacccatcaaggtgacctccaccggcaatgatccagccctcgcggacacctactcagctgaaggactcccggctgggttgaagatcaatgc cgaaactggccagattgaaggcacccctgcggttggcaacacggacgtgaagagctttgacgtcaaggtgaccttgaccgaggctgaggacggc acgggtatcccgcgcacgtcgtcgcagaccttcaagatcacccttgccccgaaccctacgccggcaccagctcccgagcctaaacctgagccta agcctgagcctacaccaaagcctgaacctaagccagagcctactccgaaacctgaacccaagccaacacctaagccagagccgaaagttgaagt tgttgttccgaatgctccggtcttcccggatgcgtctgatccggttacatgcacggttaagccgtttgtcacgctccagccgacaaagggtgta tcgtactcggtaacagttgatggcaaggagcttgactgggttgagggcaatccgtcgaggttcgaatacgactatggcaagaccgttgtggtca aggccaaggctgtcgagggcttcgagttggctaagggtgcaaagacgcagtggtcgtggactgccccgacactcgacgagctcgggtgcacaac gcccgcaccagatcctaagcctacgccagatcccaagcctactcctgatcctaagccaactcctgagcctaagccaacgccggatcccaagccg acaataatcgcccaggctaaggcgccgaagtctagcctggtccacaccggtgctacggtcgttggcctgtcggtcgctgccgcggttctgctcc tcgcaggtggtgctatcgcgattattcgccgtcgtcagggcGACTACAAAGACGATGACGACAAGtaa >SEQ_ID_NO:_108_Nuraminidase_Aida_AAMIKLKFGVFFTVLLSSAYANGTPQNITDLAAPSTAEPPASGTATTAAPTTNSPVTASSFKILNPKAEGESFEEGEEIRFQVTLKNDTDVQRAFAFQSSNLNDYQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSFTPRVTWIMRESTGHASPVEKTGEAVGKPVPVTTKLAKLSPITVTSGEGKAS YSAGDQFGYDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSAKYAVTEEDLERGEAELTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKT PNADPNLGARLTDLNILDEKTSEYNIRIPAIAVASNGDILASYDLRPLNGAWHGGDSPNENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFG WSDPSYVVDHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDTHRQTMNFALSSSTDNGRTWNSRLITNDVLSTSGTHIDEIKGCFATSGAGIQ KMHEPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFTSDTEGAPAGKHWNFDENKIAELSDGRLMLNSRIPGNSYGTGYRLVAYSADG GETWGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSNTEKPNNRVDGKVKMSYDDGKSWPIAKQIRNGHTGYTTMAVQPDGSIGLLME PTSQSVGYVNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPIKVTSTGNDPALADTYSAEGLPAGLKINAETGQIEGTPAVGNTDVKSFDVKV TLTEAEDGTGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEPTPKPEPKPEPTPKPEPKPTPKPEPKVEVVVPNAPVFPDASDPVTCTVKPFV TLQPTKGVSYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKAVEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKPTPDPKPTPEP KPTPDPKPTIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGGAIAIIRRRQGDYKDDDDK >SEQ_ID_NO:_109_Nuraminidase_Aida_DNA ATGATTAAGTTGAAATTCGGTGTGTTCTTCACAGTGTTGCTGTCGTCCGCATATGCAAATGGAACACCTCAAAATATTACTGATTTGgccgccc cgagcacagcggaaccgcctgcttcgggaacagccacaacagcggctcccactacgaattcgcccgttacagcttcgagcttcaagattctcaaccccaaagccgagggcgaaagttttgaagagggcgaggagatcagattccaggtcaccctcaagaacgacactgatgttcagcgcgcatttgccttccagagctccaacctcaacgattatcaaaaatgtaaatggtggaaagtcgaaccgggtgagactaaggaagattgcaaatttcctcaccata aagtcacagctgatgatgtagccacagggtccttcacgcctcgagtcacatggatcatgcgcgaatcaacagggcatgcttctccggttgaaaa gacaggtgaagccgttggcaaaccggttccagtgaccaccaagctcgcaaagctttcgcctatcaccgtgaccagcggagaaggtaaggcatcc tacagtgccggggatcagtttggttacgattacaccgtcacctcgctatcaaaagataagatttccgtcgagggtgaaggatgtccggctaagg agctcgatccggaaaagagcatgaagtgctcggcaaagtacgcggtcacggaggaagacctggagcgaggcgaagccgaattaactgccaaggt taaagtcagtgacgggaagcgaaacgtcactctcacagaaacaaagtcagtcaaaactcctcgggtatggccgcaggcaaaggcttttaagacg ccgaacgccgatccgaacctgggtgcccggctcaccgacctcaacattctcgatgagaagactagcgaatacaacattcgtattcccgccatcg cggttgcctccaatggtgacatcctagcttcttatgacctccgtccactcaacggagcttggcacggaggagattctccgaatgagaattccat tgtccaacgccggtcgactgacggcggcaagacctggggtccgagaaccactgtcgccgagggcaaggtcgcaggacagggaaagcgtttcggc tggtccgacccctcctacgtcgttgaccacacgactggcgagatcttcaacttccacgtcggttctcttgacgcaggtttgcctaataatcctt cctaccgtctcgtaaacggaaaagtggacgatactcaccgccagacgatgaatttcgcgttatcgtcatccacagacaacggccgcacctggaa ttcacgtctgattacgaatgatgtactcagtaccagtggtacccacatagatgaaattaaaggttgcttcgcaacgtcgggcgccggcattcag aagatgcacgagcctttcaaaggccgtctcctccagcaagcagcatgcaagttcaatactggtcgcttccgcgccatcaccatcttctcagatg accatggcaagacctggcagggtggccatttcacttcggacactgagggtgctcccgcaggcaagcactggaacttcgatgagaacaagatcgc cgaactgtccgatggtcgcctcatgctgaactcccgtatcccaggcaactcatacggaacgggttaccgtctggtagcttattctgctgatgga ggcgaaacctggggcggttatcatatcgaaaagcagcttcctgattccacaaataatgcacagctcatccgcgccttcccgtcggcaaacaacg gcacgctgcgcgcgaaggtactcctcttctctaacacggagaaaccaaacaatcgcgtcgatggtaaagtcaagatgagctacgatgacggcaa gtcttggcctatcgccaagcagattcgcaacggccatactggttacaccacgatggcggttcagcccgacggttcgatcggcctgctcatggag ccgactagccaaagcgttggctacgtgaacttcacgctcaagacgctcgctgagaatctgcctttcgaagtcgctcttgacaagattggcgatg tcaaggccaccgacggaacgccgatagcacccatcaaggtgacctccaccggcaatgatccagccctcgcggacacctactcagctgaaggact cccggctgggttgaagatcaatgccgaaactggccagattgaaggcacccctgcggttggcaacacggacgtgaagagctttgacgtcaaggtg accttgaccgaggctgaggacggcacgggtatcccgcgcacgtcgtcgcagaccttcaagatcacccttgccccgaaccctacgccggcaccag ctcccgagcctaaacctgagcctaagcctgagcctacaccaaagcctgaacctaagccagagcctactccgaaacctgaacccaagccaacacc taagccagagccgaaagttgaagttgttgttccgaatgctccggtcttcccggatgcgtctgatccggttacatgcacggttaagccgtttgtc acgctccagccgacaaagggtgtatcgtactcggtaacagttgatggcaaggagcttgactgggttgagggcaatccgtcgaggttcgaatacg actatggcaagaccgttgtggtcaaggccaaggctgtcgagggcttcgagttggctaagggtgcaaagacgcagtggtcgtggactgccccgac actcgacgagctcgggtgcacaacgcccgcaccagatcctaagcctacgccagatcccaagcctactcctgatcctaagccaactcctgagcct aagccaacgccggatcccaagccgacaataatcgcccaggctaaggcgccgaagtctagcctggtccacaccggtgctacggtcgttggcctgt cggtcgctgccgcggttctgctcctcgcaggtggtgctatcgcgattattcgccgtcgtcagggcGACTACAAAGACGATGACGACAAG >SEQ_ID_NO:_110_Neuraminidase_yebF_AA MKKRGAFLGLLLVSACASVFAANNETSKSVTFPKCEDLDAAGIAASVKRDYQQNRVARWADDQKIVGQADPVAWVSLQDIQGKDDKWSVPLTVR GKSADIHYQVSVDCKAGMAEYQRRGSGSGSPLGLWAGSGSGSKGAKMPPLKSMRKRFTRVFAGASAVALLSLGMVPAVAGAAPSTAEPPASGTA TTAAPTTNSPVTASSFKILNPKAEGESFEEGEEIRFQVTLKNDTDVQRAFAFQSSNLNDYQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSF TPRVTWIMRESTGHASPVEKTGEAVGKPVPVTTKLAKLSPITVTSGEGKASYSAGDQFGYDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSA KYAVTEEDLERGEAELTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKTPNADPNLGARLTDLNILDEKTSEYNIRIPAIAVASNGDILASY DLRPLNGAWHGGDSPNENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFGWSDPSYVVDHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDT HRQTMNFALSSSTDNGRTWNSRLITNDVLSTSGTHIDEIKGCFATSGAGIQKMHEPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFT SDTEGAPAGKHWNFDENKIAELSDGRLMLNSRIPGNSYGTGYRLVAYSADGGETWGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSN TEKPNNRVDGKVKMSYDDGKSWPIAKQIRNGHTGYTTMAVQPDGSIGLLMEPTSQSVGYVNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPI KVTSTGNDPALADTYSAEGLPAGLKINAETGQIEGTPAVGNTDVKSFDVKVTLTEAEDGTGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEP TPKPEPKPEPTPKPEPKPTPKPEPKVEVVVPNAPVFPDASDPVTCTVKPFVTLQPTKGVSYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKA VEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKPTPDPKPTPEPKPTPDPKPTIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGG AIAIIRRRQGDYKDDDDK*>SEQ_ID_NO:_111_Neuraminidase_YebF_DNAatgaaaaaaagaggggcgtttttagggctgttgttggtttctgcctgcgcatcagttttcgctgccaataatgaaaccagcaagtcggtcactt tcccaaagtgtgaagatctggatgctgccggaattgccgcgagcgtaaaacgtgattatcaacaaaatcgcgtggcgcgttgggcagatgatca aaaaattgtcggtcaggccgatcccgtggcttgggtcagtttgcaggacattcagggtaaagatgataaatggtcagtaccgctaaccgtgcgt ggtaaaagtgccgatattcattaccaggtcagcgtggactgcaaagcgggaatggcggaatatcagcggcgtGGCTCGGGCTCGGGCTCCCCAT TAGGATTATGGGCAGGATCGGGCTCCGGGTCCaaaggtgcaaagatgcccccattgaaatcgatgcgaaaacgattcacgcgagttttcgccgg cgctagtgctgtagcgttgttaagtcttggtatggttccggcggttgcaggtgcagccccgagcacagcggaaccgcctgcttcgggaacagcc acaacagcggctcccactacgaattcgcccgttacagcttcgagcttcaagattctcaaccccaaagccgagggcgaaagttttgaagagggcg aggagatcagattccaggtcaccctcaagaacgacactgatgttcagcgcgcatttgccttccagagctccaacctcaacgattatcaaaaatg taaatggtggaaagtcgaaccgggtgagactaaggaagattgcaaatttcctcaccataaagtcacagctgatgatgtagccacagggtccttc acgcctcgagtcacatggatcatgcgcgaatcaacagggcatgcttctccggttgaaaagacaggtgaagccgttggcaaaccggttccagtga ccaccaagctcgcaaagctttcgcctatcaccgtgaccagcggagaaggtaaggcatcctacagtgccggggatcagtttggttacgattacac cgtcacctcgctatcaaaagataagatttccgtcgagggtgaaggatgtccggctaaggagctcgatccggaaaagagcatgaagtgctcggca aagtacgcggtcacggaggaagacctggagcgaggcgaagccgaattaactgccaaggttaaagtcagtgacgggaagcgaaacgtcactctca cagaaacaaagtcagtcaaaactcctcgggtatggccgcaggcaaaggcttttaagacgccgaacgccgatccgaacctgggtgcccggctcac cgacctcaacattctcgatgagaagactagcgaatacaacattcgtattcccgccatcgcggttgcctccaatggtgacatcctagcttcttat gacctccgtccactcaacggagcttggcacggaggagattctccgaatgagaattccattgtccaacgccggtcgactgacggcggcaagacct ggggtccgagaaccactgtcgccgagggcaaggtcgcaggacagggaaagcgtttcggctggtccgacccctcctacgtcgttgaccacacgac tggcgagatcttcaacttccacgtcggttctcttgacgcaggtttgcctaataatccttcctaccgtctcgtaaacggaaaagtggacgatact caccgccagacgatgaatttcgcgttatcgtcatccacagacaacggccgcacctggaattcacgtctgattacgaatgatgtactcagtacca gtggtacccacatagatgaaattaaaggttgcttcgcaacgtcgggcgccggcattcagaagatgcacgagcctttcaaaggccgtctcctcca gcaagcagcatgcaagttcaatactggtcgcttccgcgccatcaccatcttctcagatgaccatggcaagacctggcagggtggccatttcact tcggacactgagggtgctcccgcaggcaagcactggaacttcgatgagaacaagatcgccgaactgtccgatggtcgcctcatgctgaactccc gtatcccaggcaactcatacggaacgggttaccgtctggtagcttattctgctgatggaggcgaaacctggggcggttatcatatcgaaaagca gcttcctgattccacaaataatgcacagctcatccgcgccttcccgtcggcaaacaacggcacgctgcgcgcgaaggtactcctcttctctaac acggagaaaccaaacaatcgcgtcgatggtaaagtcaagatgagctacgatgacggcaagtcttggcctatcgccaagcagattcgcaacggcc atactggttacaccacgatggcggttcagcccgacggttcgatcggcctgctcatggagccgactagccaaagcgttggctacgtgaacttcac gctcaagacgctcgctgagaatctgcctttcgaagtcgctcttgacaagattggcgatgtcaaggccaccgacggaacgccgatagcacccatc aaggtgacctccaccggcaatgatccagccctcgcggacacctactcagctgaaggactcccggctgggttgaagatcaatgccgaaactggcc agattgaaggcacccctgcggttggcaacacggacgtgaagagctttgacgtcaaggtgaccttgaccgaggctgaggacggcacgggtatccc gcgcacgtcgtcgcagaccttcaagatcacccttgccccgaaccctacgccggcaccagctcccgagcctaaacctgagcctaagcctgagcct acaccaaagcctgaacctaagccagagcctactccgaaacctgaacccaagccaacacctaagccagagccgaaagttgaagttgttgttccga atgctccggtcttcccggatgcgtctgatccggttacatgcacggttaagccgtttgtcacgctccagccgacaaagggtgtatcgtactcggt aacagttgatggcaaggagcttgactgggttgagggcaatccgtcgaggttcgaatacgactatggcaagaccgttgtggtcaaggccaaggct gtcgagggcttcgagttggctaagggtgcaaagacgcagtggtcgtggactgccccgacactcgacgagctcgggtgcacaacgcccgcaccag atcctaagcctacgccagatcccaagcctactcctgatcctaagccaactcctgagcctaagccaacgccggatcccaagccgacaataatcgc ccaggctaaggcgccgaagtctagcctggtccacaccggtgctacggtcgttggcctgtcggtcgctgccgcggttctgctcctcgcaggtggt gctatcgcgattattcgccgtcgtcagggcGACTACAAAGACGATGACGACAAGtaa >SEQ_ID_NO:_112_Nuraminidase_FliC_AA MAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAGGSGSGSPLGLWAGSGSGSAAPSTAEPPASGTATTAAPTTNSPVTASS FKILNPKAEGESFEEGEEIRFQVTLKNDTDVQRAFAFQSSNLNDYQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSFTPRVTWIMRESTGHA SPVEKTGEAVGKPVPVTTKLAKLSPITVTSGEGKASYSAGDQFGYDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSAKYAVTEEDLERGEAE LTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKTPNADPNLGARLTDLNILDEKTSEYNIRIPAIAVASNGDILASYDLRPLNGAWHGGDSP NENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFGWSDPSYVVDHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDTHRQTMNFALSSSTDN GRTWNSRLITNDVLSTSGTHIDEIKGCFATSGAGIQKMHEPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFTSDTEGAPAGKHWNFD ENKIAELSDGRLMLNSRIPGNSYGTGYRLVAYSADGGETWGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSNTEKPNNRVDGKVKMS YDDGKSWPIAKQIRNGHTGYTTMAVQPDGSIGLLMEPTSQSVGYVNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPIKVTSTGNDPALADTY SAEGLPAGLKINAETGQIEGTPAVGNTDVKSFDVKVTLTEAEDGTGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEPTPKPEPKPEPTPKPE PKPTPKPEPKVEVVVPNAPVFPDASDPVTCTVKPFVTLQPTKGVSYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKAVEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKPTPDPKPTPEPKPTPDPKPTIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGGAIAIIRRRQGDYKDDDDK >SEQ_ID_NO:_113_Nuraminidase_FliC_DNA gggaataaggggcagagaaaagagtatttcggcgactaacaaaaaatggctgtttttgaaaaaaattctaaaggttgttttacgacagacgata acagggttgacggcgattgagccgacgggtggaaacccaatacgtaatcaacgacttgcaatataggataacgaatcatggcacaagtcattaa taccaacagcctctcgctgatcactcaaaataatatcaacaagaaccagtctgcgctgtcgagttctatcgagcgtctgtcttctggcttgcgt attaacagcgcgaaggatgacgcagcgggtGGCTCGGGCTCGGGCTCCCCATTAGGATTATGGGCAGGATCGGGCTCCGGGTCCgccgccccga gcacagcggaaccgcctgcttcgggaacagccacaacagcggctcccactacgaattcgcccgttacagcttcgagcttcaagattctcaaccc caaagccgagggcgaaagttttgaagagggcgaggagatcagattccaggtcaccctcaagaacgacactgatgttcagcgcgcatttgccttc cagagctccaacctcaacgattatcaaaaatgtaaatggtggaaagtcgaaccgggtgagactaaggaagattgcaaatttcctcaccataaag tcacagctgatgatgtagccacagggtccttcacgcctcgagtcacatggatcatgcgcgaatcaacagggcatgcttctccggttgaaaagac aggtgaagccgttggcaaaccggttccagtgaccaccaagctcgcaaagctttcgcctatcaccgtgaccagcggagaaggtaaggcatcctac agtgccggggatcagtttggttacgattacaccgtcacctcgctatcaaaagataagatttccgtcgagggtgaaggatgtccggctaaggagc tcgatccggaaaagagcatgaagtgctcggcaaagtacgcggtcacggaggaagacctggagcgaggcgaagccgaattaactgccaaggttaaagtcagtgacgggaagcgaaacgtcactctcacagaaacaaagtcagtcaaaactcctcgggtatggccgcaggcaaaggcttttaagacgccgaacgccgatccgaacctgggtgcccggctcaccgacctcaacattctcgatgagaagactagcgaatacaacattcgtattcccgccatcgcgg ttgcctccaatggtgacatcctagcttcttatgacctccgtccactcaacggagcttggcacggaggagattctccgaatgagaattccattgt ccaacgccggtcgactgacggcggcaagacctggggtccgagaaccactgtcgccgagggcaaggtcgcaggacagggaaagcgtttcggctgg tccgacccctcctacgtcgttgaccacacgactggcgagatcttcaacttccacgtcggttctcttgacgcaggtttgcctaataatccttcct accgtctcgtaaacggaaaagtggacgatactcaccgccagacgatgaatttcgcgttatcgtcatccacagacaacggccgcacctggaattc acgtctgattacgaatgatgtactcagtaccagtggtacccacatagatgaaattaaaggttgcttcgcaacgtcgggcgccggcattcagaag atgcacgagcctttcaaaggccgtctcctccagcaagcagcatgcaagttcaatactggtcgcttccgcgccatcaccatcttctcagatgacc atggcaagacctggcagggtggccatttcacttcggacactgagggtgctcccgcaggcaagcactggaacttcgatgagaacaagatcgccga actgtccgatggtcgcctcatgctgaactcccgtatcccaggcaactcatacggaacgggttaccgtctggtagcttattctgctgatggaggc gaaacctggggcggttatcatatcgaaaagcagcttcctgattccacaaataatgcacagctcatccgcgccttcccgtcggcaaacaacggca cgctgcgcgcgaaggtactcctcttctctaacacggagaaaccaaacaatcgcgtcgatggtaaagtcaagatgagctacgatgacggcaagtcttggcctatcgccaagcagattcgcaacggccatactggttacaccacgatggcggttcagcccgacggttcgatcggcctgctcatggagccgactagccaaagcgttggctacgtgaacttcacgctcaagacgctcgctgagaatctgcctttcgaagtcgctcttgacaagattggcgatgtca aggccaccgacggaacgccgatagcacccatcaaggtgacctccaccggcaatgatccagccctcgcggacacctactcagctgaaggactccc ggctgggttgaagatcaatgccgaaactggccagattgaaggcacccctgcggttggcaacacggacgtgaagagctttgacgtcaaggtgacc ttgaccgaggctgaggacggcacgggtatcccgcgcacgtcgtcgcagaccttcaagatcacccttgccccgaaccctacgccggcaccagctc ccgagcctaaacctgagcctaagcctgagcctacaccaaagcctgaacctaagccagagcctactccgaaacctgaacccaagccaacacctaa gccagagccgaaagttgaagttgttgttccgaatgctccggtcttcccggatgcgtctgatccggttacatgcacggttaagccgtttgtcacg ctccagccgacaaagggtgtatcgtactcggtaacagttgatggcaaggagcttgactgggttgagggcaatccgtcgaggttcgaatacgact atggcaagaccgttgtggtcaaggccaaggctgtcgagggcttcgagttggctaagggtgcaaagacgcagtggtcgtggactgccccgacact cgacgagctcgggtgcacaacgcccgcaccagatcctaagcctacgccagatcccaagcctactcctgatcctaagccaactcctgagcctaag ccaacgccggatcccaagccgacaataatcgcccaggctaaggcgccgaagtctagcctggtccacaccggtgctacggtcgttggcctgtcgg tcgctgccgcggttctgctcctcgcaggtggtgctatcgcgattattcgccgtcgtcagggcGACTACAAAGACGATGACGACAAGtaaatgat ttttctcatgacgaaagattcttttcttttacagggcttttggcagttgaaagataatcacgaaatgataaaaatcaattccctgtcagagatc aaaaaagtaggcaataaacccttcaaggttatcattgatacctatcacaatcatatccttgatgaagaagcgattaaatttctggagaaattag atgccgagagaattattgttttggcaccttatcacatcagtaaactaaaagctaaagcgcctatttattttgttagccgcaaagaaagtatcaa aaatcttcttgagattacttatggtaaacacttgccccataagaattcacaattatgtttttcacataatcagttcaaaattatgcaactgatt ctgaaaaataaaaatgaaagcaatatcacgtcgacgctcaatatttcgcaacaaacattaaagattcagaaattcaacattatgtacaagctga aactaagacgtatgagcgacatcgtcaccctgggtatcacatcttatttttag >SEQ_ID_NO:_114_Neuraminidase_Usp45_AA MKKKIISAILMSTVILSAAAPLSGVYAAPSTAEPPASGTATTAAPTTNSPVTASSFKILNPKAEGESFEEGEEIRFQVTLKNDTDVQRAFAFQS SNLNDYQKCKWWKVEPGETKEDCKFPHHKVTADDVATGSFTPRVTWIMRESTGHASPVEKTGEAVGKPVPVTTKLAKLSPITVTSGEGKASYSA GDQFGYDYTVTSLSKDKISVEGEGCPAKELDPEKSMKCSAKYAVTEEDLERGEAELTAKVKVSDGKRNVTLTETKSVKTPRVWPQAKAFKTPNA DPNLGARLTDLNILDEKTSEYNIRIPAIAVASNGDILASYDLRPLNGAWHGGDSPNENSIVQRRSTDGGKTWGPRTTVAEGKVAGQGKRFGWSD PSYVVDHTTGEIFNFHVGSLDAGLPNNPSYRLVNGKVDDTHRQTMNFALSSSTDNGRTWNSRLITNDVLSTSGTHIDEIKGCFATSGAGIQKMH EPFKGRLLQQAACKFNTGRFRAITIFSDDHGKTWQGGHFTSDTEGAPAGKHWNFDENKIAELSDGRLMLNSRIPGNSYGTGYRLVAYSADGGET WGGYHIEKQLPDSTNNAQLIRAFPSANNGTLRAKVLLFSNTEKPNNRVDGKVKMSYDDGKSWPIAKQIRNGHTGYTTMAVQPDGSIGLLMEPTS QSVGYVNFTLKTLAENLPFEVALDKIGDVKATDGTPIAPIKVTSTGNDPALADTYSAEGLPAGLKINAETGQIEGTPAVGNTDVKSFDVKVTLT EAEDGTGIPRTSSQTFKITLAPNPTPAPAPEPKPEPKPEPTPKPEPKPEPTPKPEPKPTPKPEPKVEVVVPNAPVFPDASDPVTCTVKPFVTLQ PTKGVSYSVTVDGKELDWVEGNPSRFEYDYGKTVVVKAKAVEGFELAKGAKTQWSWTAPTLDELGCTTPAPDPKPTPDPKPTPDPKPTPEPKPT PDPKPTIIAQAKAPKSSLVHTGATVVGLSVAAAVLLLAGGAIAIIRRRQGDYKDDDDK* >SEQ_ID_NO:_115_Neuraminidase_Usp45_DNA ATGAAAAAGAAAATTATCTCAGCCATTTTGATGTCAACAGTCATCCTTTCAGCGGCTGCACCTTTGTCTGGTGTTTATGCTGCTCCTAGCACTG CTGAACCACCTGCTTCAGGCACAGCAACTACTGCTGCACCAACTACTAATAGCCCAGTAACGGCTTCATCTTTTAAAATTCTTAATCCCAAAGC TGAAGGCGAATCATTTGAAGAAGGGGAAGAAATTCGATTTCAAGTTACTTTGAAAAACGATACTGACGTTCAACGCGCATTTGCTTTTCAATCA TCAAATCTTAACGACTACCAAAAATGCAAATGGTGGAAAGTTGAACCAGGTGAAACAAAAGAAGATTGTAAATTTCCACATCACAAAGTGACTG CTGATGACGTTGCTACAGGTTCATTCACACCACGTGTTACATGGATTATGCGTGAATCTACTGGCCACGCGTCTCCTGTTGAAAAAACTGGTGA AGCCGTAGGTAAACCAGTACCTGTGACAACAAAATTGGCTAAACTTTCACCTATCACAGTAACTTCAGGAGAAGGTAAAGCTTCATATTCTGCA GGAGATCAATTTGGTTATGATTATACAGTTACATCTCTTAGTAAAGACAAGATCAGCGTAGAAGGTGAAGGCTGTCCAGCTAAAGAATTAGATC CAGAAAAATCTATGAAATGTAGTGCTAAATACGCTGTTACCGAAGAGGATCTTGAACGTGGAGAAGCAGAATTGACAGCCAAAGTTAAAGTCTC TGATGGAAAACGTAATGTAACTCTTACAGAAACAAAATCAGTTAAAACTCCACGTGTTTGGCCACAAGCTAAAGCATTTAAAACTCCAAATGCA GACCCTAACCTTGGTGCACGCCTGACTGATCTTAATATCCTCGACGAAAAAACATCTGAATATAATATTCGTATTCCTGCAATTGCTGTTGCTA GCAATGGAGATATTCTTGCTTCTTACGATCTCCGTCCACTCAATGGCGCATGGCACGGCGGTGACTCACCAAACGAAAATTCAATTGTTCAACG TCGTTCAACTGATGGTGGAAAAACTTGGGGTCCACGCACTACAGTTGCTGAAGGTAAAGTTGCGGGTCAAGGAAAACGTTTTGGTTGGTCAGAT CCATCTTACGTTGTTGACCATACTACAGGAGAAATCTTCAATTTTCACGTAGGTTCATTGGATGCGGGTTTGCCAAATAACCCTAGCTATCGTC TTGTCAACGGAAAAGTTGATGATACGCACCGCCAAACAATGAACTTCGCATTATCTTCTTCAACTGATAACGGCCGTACTTGGAATTCACGTTT GATTACAAATGATGTTTTGTCAACTTCTGGTACACACATTGATGAAATTAAAGGCTGTTTCGCAACATCAGGTGCTGGAATTCAAAAAATGCAC GAACCTTTCAAAGGTCGTCTTTTGCAACAAGCGGCATGTAAATTTAACACAGGACGTTTCCGTGCGATTACTATTTTTTCAGACGATCACGGTA AGACATGGCAAGGTGGTCATTTTACTTCAGATACTGAGGGAGCCCCAGCCGGTAAACATTGGAACTTCGATGAAAATAAAATCGCCGAATTGTCAGATGGACGTTTGATGCTTAACTCACGAATCCCAGGGAACTCATACGGTACAGGATACCGTCTTGTTGCTTACTCAGCTGACGGTGGTGAAACATGGGGAGGATATCATATTGAAAAACAACTTCCAGATTCAACAAACAACGCACAATTGATCCGTGCATTTCCTTCAGCTAACAACGGAACTTTGC GTGCAAAGGTACTCTTGTTCTCAAATACCGAGAAACCAAACAATCGTGTCGACGGGAAAGTTAAAATGTCTTATGATGATGGGAAGTCATGGCC AATTGCTAAACAAATTCGTAACGGACACACAGGTTACACAACTATGGCTGTTCAACCAGATGGTTCAATTGGTTTGCTTATGGAACCAACAAGT CAAAGCGTTGGTTATGTCAATTTTACTCTCAAAACTTTGGCCGAAAACCTTCCATTTGAAGTAGCTTTGGATAAAATCGGAGACGTAAAAGCAA CGGATGGTACTCCAATCGCACCAATTAAAGTTACTTCTACAGGCAACGATCCTGCACTTGCTGATACTTACTCAGCGGAAGGTCTTCCTGCTGG ACTCAAAATTAACGCAGAAACAGGACAAATCGAAGGTACTCCAGCTGTTGGAAACACTGATGTAAAATCATTTGATGTTAAAGTTACACTTACA GAAGCAGAAGATGGTACAGGTATTCCACGTACTAGTAGCCAAACATTCAAAATCACACTTGCTCCTAATCCAACACCAGCACCTGCTCCAGAAC CAAAACCAGAACCTAAACCAGAACCTACACCAAAACCTGAGCCAAAACCAGAACCAACACCAAAACCTGAACCTAAACCAACTCCAAAGCCAGA ACCTAAAGTTGAAGTTGTTGTTCCTAATGCCCCAGTTTTTCCAGATGCTAGTGATCCAGTCACTTGCACTGTAAAACCATTTGTAACTTTACAA CCAACAAAAGGTGTATCATACTCTGTAACTGTGGATGGCAAAGAACTTGATTGGGTTGAAGGTAATCCTTCTCGTTTCGAATACGATTATGGTA AAACTGTTGTAGTGAAAGCTAAAGCCGTTGAGGGATTTGAATTGGCCAAGGGTGCGAAGACTCAATGGTCATGGACTGCACCTACTTTAGACGA ATTAGGTTGTACTACACCAGCTCCAGATCCTAAGCCTACTCCAGACCCTAAACCAACACCTGATCCAAAGCCTACACCAGAACCAAAACCTACT CCAGATCCTAAACCAACTATCATTGCTCAAGCCAAAGCTCCTAAAAGTTCTCTTGTTCACACAGGTGCCACTGTAGTTGGACTTAGCGTTGCTG CAGCAGTACTTCTTTTAGCTGGAGGTGCTATTGCTATCATTCGTCGACGCCAAGGAGATTACAAAGACGACGACGACAAATAA >SEQ_ID_NO:_116_MMP_AA GSGSGSPLGLWAGSGSGS >SEQ_ID_NO:_117_MMP_DNA ggCTCGGGCTCGGGCTCCCCATTAGGATTATGGGCAGGATCGGGCTCCGGGTCC Examples Example 1 - in vivo tolerability and biodistribution study of a candidate E.coli K12 strain in 4T1 tumour bearing mice A candidate Escherichia coli K12 MG1655 strain was engineered to express bioluminescent bioreporters using bacterial luxCDABE luciferase operons as described by Fedorec et al., 2019, “Two New Plasmid Post-segregational Killing Mechanisms for the Implementation of Synthetic Gene Networks in Escherichia coli”, iScience, 14:323-334 (herein incorporated by reference in its entirety). Tumours were induced in healthy female BALB / c mice at 6-7 weeks old at reception, obtained from Charles River. BALB / c mice were anaesthetized with isofluorane and 1x1054T1 breast cells suspended in a volume of 50 µL RPMI 1640 medium was injected into the MFP tissue (right upper udder). The candidate Escherichia coli K12 MG1655 strain was administrated in PBS to 4T1 tumour bearing mice at doses of 106CFU, 107CFU and 108CFU per mouse by intravenous injection into the caudal vein. All 3 doses were tolerated during the 6 days observation post- administration. One mouse was terminated one day post administration because of tumour necrosis in Group 5 - Heat killed bacteria at 108CFU. As can be seen in Figure 1, mice administered the candidate Escherichia coli K12 MG1655 strain at a dose of 106CFU and 107CFU maintained mean body weights comparable to those of mice administered the vehicle alone. The higher dose of 108CFU per mouse caused higher weight loss. Mice were imaged at 24 h, 48 h, and 72 h post-administration (p.a.) using the Photoimager Optima in vivo Imaging System. During all the acquisitions, mice were continuously anaesthetized using isoflurane (Minerve, France) in a mixture of oxygen via a nose piece. As shown in Figure 2, luminescence was localised in the tumour at 48 h and 72 h post- administration in mice administered with 106and 107CFU doses, and can be seen at 6 days post-administration (data not shown). Luminescence was localised in the tumour at 24 h p.a. in mice administered with a 108CFU dose. In view of the weight loss in the group administered 108CFU of the candidate strain, the level of colonisation in the tumour and secondary organs was quantified in mice administered a dose of 107CFU at 72 h post-administration. The candidate was administrated by intravenous injection into the caudal vein at 107CFU dose. Mice were sacrificed and imaged at 72 h post-administration, and organs were collected for CFU counting in line with Kang et al., 2020 “Imaging of tumor colonization by Escherichia coli using18F-FDS PET”, Theranostics, 10(11):4958-4966 (herein incorporated by reference in its entirety). As shown in Figure 3A, luminescence was localised in the tumour. CFU counting showed high concentration (108CFU / g tissue) of bacteria in the tumour with residual level (around or below 104CFU / g tissue) of bacteria in secondary organs. This study demonstrates that the candidate Escherichia coli K12 MG1655 strain is well- tolerated and localises to and accumulates in tumours in a mouse tumour model. Example 2 – Developing a strain of extracellular-matrix (ECM)-degrading bacteria Several components of the extracellular matrix (ECM) have been identified as important in preventing immune cell infiltration into solid tumours. Hyaluronic Acid (HA) is particularly important in this context. It is a highly hygroscopic glycosaminoglycan, which expands when hydrated, leading to high interstitial pressure and a collapsed vasculature. It is degraded by different forms of naturally occurring enzymes called hyaluronidases. The present study therefore focussed on generating a hyaluronidase-producing bacterial strain that could be deployed in vivo. A hyaluronidase-producing bacterial in the candidate Escherichia coli K12 MG1655 strain was engineered using BASIC, a modular DNA assembly method developed by Prof Geoff Baldwin at Imperial College London. The method uses oligo linkers to join together multiple DNA bioparts at once (Storch et al., 2015, “BASIC: A New Biopart Assembly Standard for Idempotent Cloning Provides Accurate, Single-Tier DNA Assembly for Synthetic Biology”, ACS Synth. Biol., 4:781-787; herein incorporated by reference in its entirety). The turbidimetric cetyltrimethylammonium method disclosed by Oueslati et al. 2014, “CTAB turbidimetric method for assaying hyaluronic acid in complex environments and under cross-linked form”, Carbohydrate polymers, 112:102-108 (herein incorporated by reference in its entirety) was used to assess the hyaluronic acid degrading ability of the candidate Escherichia coli K12 MG1655 strain. In this method, the cetyltrimethylammonium bromide interacts with hyaluronic acid present in a solution, causing the solution to become cloudy, leading to a high OD600 value when spectrophotometrically analysed. When the hyaluronic acid is degraded, the solution becomes clearer, and the observed OD600 value decreases. Candidate Escherichia coli K12 MG1655 engineered as discussed in Example 3 below to express a secreted bacterial hyaluronidase (for example, SEQ ID NO: 1 or SEQ ID NO: 37) (Escherichia coli K12 MG1655 PelB-bH) under the control of a rhamnose-inducible promoter was cultured in LB media supplemented with 0.4 mg / mL purified hyaluronan (“No induction” condition) or LB media supplemented with 0.4 mg / mL purified hyaluronan and 0.2% (w / v) rhamnose (“Induced” condition). A third condition (“Media”) contained only LB media supplemented with 0.4 mg / mL purified hyaluronan. The OD600 of the media in each condition was measured over 6 h. As shown in Figure 4, purified hyaluronic acid was degraded by Escherichia coli K12 MG1655 bH when expression of the bacterial hyaluronidase was induced. Escherichia coli K12 MG1655 bH was then tested in a patient-derived tissue explant as disclosed in Puttock et al., 2023, “Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis”, Nat. Commun., 14:2514 (herein incorporated by reference in its entirety), which maintains the native extracellular matrix (ECM) structure and composition. Escherichia coli K12 MG1655 constitutively expressing GFP were inoculated into the decellularized tissue explant and incubated for up to 5 h. The tissue explant was imaged using fluorescence microscopy at hourly intervals for up to 5 h, and the depth of infiltration into the tissue was measured. As shown in Figure 5, Escherichia coli K12 MG1655 were capable of invading the extracellular matrix over a 5 h time-period. A 3D z-stack shows bacteria (white; indicated by white arrows) infiltration of the bacteria into the matrix (stained with fibronectin (FN1), a major component of fibrotic tissue to visualize general tissue architecture). To test the ability of the hyaluronidase-producing bacteria to degrade extracellular matrix (ECM) in the model, 107CFU Escherichia coli K12 MG1655 bH was incubated with decellularized tissue explant material in the presence or absence of the bH expression inducer molecule, rhamnose. After 4 h, the explant material was stained using hyaluronic acid binding protein (IHC; Sigma Aldrich, Catalogue No. 385911), and imaged using light microscopy. As shown in Figure 5, tissue explants incubated with tissue explants incubated with Escherichia coli K12 MG1655 bH completely lose all hyaluronic acid staining. Finally, the ability of hyaluronidase-producing bacteria to potentiate immunotherapy was tested using a tumour killing assay developed in the academic lab. Briefly, patient-derived tissues containing cancer cells were treated with either Escherichia coli K12 MG1655 bH in media (DMEM supplemented with 10% FBS, 1% L-glucose, 1x kanamycin and 0.2% rhamnose) or media alone. Cancer-reactive T-cells (T4), unreactive T-cells (UT), or media alone were then added. As shown in Figure 7, treatment of the tissues with Escherichia coli K12 MG1655 bH in led to a significant increase in the killing of cancer cells by cancer- reactive T-cells (labelled “T4 + Bac”), compared to when no bacterial treatment step was applied. Accordingly, this study demonstrates that the inventors have successfully generated a bacterial strain capable of inducibly expressing the extracellular matrix (ECM) degrading polypeptide, hyaluronidase. The bacterium can invade and degrade extracellular matrix in a decellularized tissue explant; and shows synergistic effects with cancer-reactive T-cells. Example 3 – Developing a secreted extracellular matrix (ECM) degrading polypeptide Bacterial secretion systems are protein complexes present on the cell membranes. They can be classified into two different mechanisms. First, a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and secreted directly outside the bacterial cell, which is found in both gram-negative and gram-positive bacteria. The second involves a two-step mechanism found in gram-negative bacteria only in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally secreted outside the bacterial cell. A fusion protein containing a bacterial hyaluronidase fused to a PelB signal sequence at its N-terminus was cloned into Escherichia coli K12 MG1655 (Escherichia coli K12 MG1655 PelB-bH), under the control of a rhamnose-inducible promoter. Escherichia coli K12 MG1655 PelB-bH was incubated in media, with or without 0.2% (w / v) rhamnose for 4 h. Escherichia coli K12 MG1655 expressing GFP was incubated in the same conditions, as a negative control. Following incubation, supernatant and pellet were separated, and 0.8 mg / ml of hyaluronic acid was added to each sample. The mixtures were incubated 18h at 37 degrees and the level of hyaluronan degradation was assessed using the cetyltrimethylammonium bromide turbidimetric method (CTM) as discussed above. As shown in Figure 8A, supernatant collected from Escherichia coli K12 MG1655 PelB-bH incubated with 0.2% rhamnose (“induced” conditions) was capable of degrading hyaluronic acid, whereas hyaluronic acid added to supernatant collected from Escherichia coli K12 MG1655 PelB-bH incubated in “uninduced” conditions was not degraded. Figure 8B shows that bacterial hyaluronidase was detectable in the supernatant of Escherichia coli K12 MG1655 PelB-bH incubated in “induced” conditions but not in “uninduced” conditions, as detected by western blot. A fusion protein containing a bacterial neuraminidase fused to a PelB signal sequence at its N-terminus was cloned into Escherichia coli K12 MG1655 (Escherichia coli K12 MG1655 PelB-Nh), under the control of a rhamnose-inducible promoter. Escherichia coli K12 MG1655 PelB-Nh was incubated in media with 0.2% (w / v) rhamnose for 4 h. Escherichia coli K12 MG1655 expressing GFP was incubated in the same conditions, as a negative control. Following incubation, supernatant and pellet were separated, and supernatant was tested for the detection of neuraminidase using a Neuraminidase Assay Kit (Abcam, ab138888). As shown in Figure 8C, supernatant collected from Escherichia coli K12 MG1655 PelB-Nh was capable of degrading terminal sialic acid residues and neuraminic acids, whereas Escherichia coli K12 MG1655 GFP did not show any neuraminidase activity. A fusion protein containing a bacterial neuraminidase (NH) fused at its N-terminus to a secretion system signal sequence selected from a PelB signal sequence, a carrier protein YebF, and a T3SS (FliC) and an autotransporter (AIDAc) was cloned into Escherichia coli K12 MG1655, under the control of a rhamnose-inducible promoter. Escherichia coli K12 MG1655 PelB-NH, Escherichia coli MG1655 yebF-NH, Escherichia coli MG1655 FliC-NH and Escherichia coli MG1655 AidaC-NH were each incubated in media supplemented with 0.2% (w / v) rhamnose and 2.5 µg / ml of human matrix metalloproteinase 1 (MMP1) for 4 h. Escherichia coli K12 MG1655 transformed with an empty vector (Evec) was incubated in the same conditions, as a negative control. Following incubation, supernatant and pellet were separated, and supernatant was tested for the detection of neuraminidase using Neuraminidase Assay Kit (Abcam, ab138888). As shown in Figure 8D, the YebF, FliC, and AidaC lead to the secretion of active neuraminidase into the supernatant. Treatment with MMP to release secreted NH from the associated secretion signal increases the neuraminidase activity of NH secreted under the control of YebF, FliC, and AidaC. Example 4 – Development of pH-inducible and hypoxia-inducible promoters Engineering bacteria as a vector for therapeutic payload delivery requires the development of tumour microenvironment biosensors. Some bacteria are naturally capable of sensing the low oxygen and acidic pH levels that are present in the tumour microenvironment. Several promoters have been identified to be activated only when the bacteria are inside the tumour core. Such exemplary promoters are set out in Table 2. Table 2 Promoter Origin Sensor Reference pflE Salmonella Hypoxia Arrach et al., 2008, “Salmonella promoters Typhimurium preferentially activated inside tumors”, Cancer Res., 68(12):4827-32 Stm1787 Low pH Flentie et al., 2012, “A bioluminescent transposon reporter-trap identifies tumor- specific microenvironment-induced promoters in Salmonella for conditional bacterial-based tumor therapy.” Cancer Discov., 2(7):624-37 pepT Hypoxia Mengesha et al., 2006, “Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated Salmonella” Cancer biology & therapy, 5(9), 1120-8. YbiY E. coli Hypoxia pflE-like hyaA Low pH Stm1787-like pvhb Vitreoscilla Hypoxia Tsai et al., 1995, “Fnr, a global transcriptional regulator of Escherichia coli, activates the Vitreoscilla hemoglobin (VHb) promoter and intracellular VHb expression increases cytochrome d promoter activity” Biotechnol Prog., 11(3):288-93. P1 L. lactis Low pH Madsen et al., 2005, “Two acid-inducible promoters from Lactococcus lactis require the cis-acting ACiD-box and the transcription regulator RcfB” Mol. Microbiol., 56: 735-746. P2 Low pH Madsen et al., 2005 Candidate pH-inducible and hypoxia-inducible promoters were generated by synthesising the promoter DNA sequence with linkers (including linkers encoding an RBS) using the method set out in Storch et al., 2015, “BASIC: A New Biopart Assembly Standard for Idempotent Cloning Provides Accurate, Single-Tier DNA Assembly for Synthetic Biology”, ACS Synth. Biol., 4:781-787 (herein incorporated by reference in its entirety). This approach led to five test promoters – LOR7, LOR9, LOR1, LPR7, and LPR1 – that were tested for hypoxia-inducible and pH-inducible promoter activity. Test constructs encoding GFP under the control of the test promoters were cloned into Escherichia coli K12 MG1655; and a control strain constitutively expressing GFP was generated. Bacteria were cultured in media to mid-exponential phase. The bacteria were then resuspended in media at pH 7 and pH 6; and added in 96-well microplates. Hypoxia conditions were created by adding mineral oil on top of wells. The plate was incubated for 18 h at 37°C and the level of fluorescence was measured using a microplate reader. As shown in Figure 9A and 9B, LOR9, LOR1, and LPR1 promoters show induction in hypoxic conditions. Of these, LOR9 and LOR1 show tight repression of GFP expression in normoxic condition; and show increased expression of GFP in hypoxic conditions at pH 6. Accordingly, LOR9 and LOR1 represent promoters that are specifically induced in the tumour microenvironment. PelB-bH was placed under the control of LOR7 and LOR9 in Escherichia coli K12 MG1655 to determine whether these promoters are capable of driving degradation of hyaluronic acid in conditions that recapitulate the tumour microenvironment. Escherichia coli K12 MG1655 LOR7-PelB-bH, Escherichia coli K12 MG1655 LOR9-PelB-bH, and Escherichia coli K12 MG1655 constitutively expressing GFP were cultured in media to mid-exponential phase and resuspended in media at pH 7 and pH 6, supplemented with 0.4 mg / ml hyaluronic acid and placed in a 96-well microplate. Cells were cultured in normoxic conditions or hypoxic conditions created by adding mineral oil on top of the wells. The plate was incubated for 18h at 37 degrees and the level of hyaluronan degradation was assessed using the cetyltrimethylammonium bromide turbidimetric method (CTM). As shown in Figure 9C, LOR9 activity is increased in tumour physiological conditions (low oxygen and pH). Example 5 – in vivo activity of tumour-inducible secreted hyaluronidase Candidate Escherichia coli K12 derivative strain was engineered to secrete Hyaluronidase degrading enzymes under the control of tumour-inducible promoters LO_R7 and LO_R9 responding to low level of oxygen in the tumour microenvironment as provided herein. An additional control strain was engineered to secrete Hyaluronidase under a constitutive promoter. Tumours were induced in healthy female BALB / c and C57BL / 6 mice, 6-7 weeks old at reception, orthotopically injected with 5 x 1044T1 and E0771 cells, respectively, under the mammary fat pad. Once the tumours reached an average size of 150 mm3, mice were randomized according to tumour size into the following treatment groups: PBS (control group), LO R7 106CFUs (live BioThx group), LO R9 106CFUs (live BioThx group), constitutive 106CFUs (live BioThx group), ICI (immunotherapy group) and LO R7106CFUs + ICI (combination therapy group). Mice received either a single i.v. injection of the live BioThx (106CFUs / mouse) or PBS and after three (for the 4T1 study) or four days (for the E0771 study), they received the first cycle of immunotherapy via an i.p. injection (10 mg / kg anti-PD-1 + 5 mg / kg anti-CTLA-4). In total mice were subjected to three cycles of ICI treatment, with a three-day interval between each. Tumors were collected and processed accordingly for the flow cytometry experiment, and the survival of mice was monitored daily. Tumour stiffness and perfusion were measured at 0, 3, and 6 days post-administration with the ultrasound-based methods of shear wave elastography (SWE) and contrast enhanced ultrasound (CEUS), respectively. Administration of bacteria constitutively expressing hyaluronidase or expressing hyaluronidase under the control of the LOR7 or LOR9 promoter to tumour bearing mice has been shown to reduce ECM stiffness in the tumour and increase vascular perfusion (Figures 10A-B), and a significant degradation of hyaluronan levels in the TME was also observed (Figure 10C). For both 4T1 and E0771 combination studies, the tumour dimensions were measured every 2 to 3 days with a calliper until their surgical resection 2 days post-last immunotherapy cycle. Results showed that E. coli expressing hyaluronidase under the control of the LO R7 promoter (also denoted C35R7) potentiates the efficacy of immunotherapy in a non- responding mouse model of triple negative breast cancer after three cycles of ICI administered every 3-days (Figures 11 and 12). After analysing the immune profile of the TME following treatments by flow cytometry, the results showed a reduction in the myeloid- derived suppressor cell (MDSC, CD45+GR1+CD11b+) population in both 4T1 and E0771 tumors treated with ICI alone or combination therapy, while the levels of total lymphocyte remained unchanged across the different treatment groups suggesting a shift from an immunosuppressive to an immunosupportive microenvironment (Figure 13). Equivalents The foregoing embodiments, instances, and examples are applicable to any of the aspects of the present disclosure and should be construed as such. While the present disclosure has been described in terms of various aspects, embodiments, and examples, it is understood that variations, improvements, and equivalents will occur to the person skilled in the art. Such variations, improvements, and equivalents are contemplated by the present disclosure and fall within the scope of the matter disclosed and claimed herein. References All references to other documents made in the present application, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically herein incorporated by reference.

Claims

Claims 1. A recombinant bacterial cell capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component, wherein: the cell comprises a nucleic acid comprising a nucleotide sequence that encodes the heterologous extracellular matrix (ECM) degrading polypeptide and a promoter; wherein the nucleotide sequence that encodes the heterologous extracellular matrix (ECM) degrading polypeptide is operably linked to the promoter; and the promoter is a tumour-inducible promoter.

2. The recombinant bacterial cell of claim 1, wherein the heterologous extracellular matrix (ECM) degrading polypeptide is secreted from the cell.

3. A recombinant bacterial cell capable of expressing a heterologous extracellular matrix (ECM) degrading polypeptide that degrades an extracellular matrix component, wherein the cell comprises a nucleic acid comprising a nucleotide sequence that encodes the heterologous extracellular matrix (ECM) degrading polypeptide, wherein the heterologous extracellular (ECM) degrading polypeptide is secreted from the cell.

4. The recombinant bacterial cell of claim 3, wherein the nucleic acid further comprises a promoter; optionally wherein the nucleotide sequence encoding the heterologous extracellular matrix degrading (ECM) polypeptide is operably linked to the promoter and wherein the promoter is a tumour-inducible promoter.

5. The recombinant bacterial cell of any one of claims 1-4, wherein: i) the extracellular matrix degrading polypeptide is: a) a hyaluronidase; b) a microbial hyaluronidase or a mammalian hyaluronidase; c) a bacterial hyaluronidase; d) chondroitin ABC lyase; e) a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; e) a bacterial chondroitin ABC lyase; f) neuraminidase; g) a microbial neuraminidase or a mammalian neuraminidase; h) a bacterial neuraminidase;i) PNGase; j) a microbial PNGase or a mammalian PNGase; k) a bacterial PNGase; optionally wherein the extracellular matrix component is a proteoglycan; ii) the ECM component is hyaluronic acid (HA) and the ECM degrading polypeptide is: a) a hyaluronidase; b) a microbial hyaluronidase or a mammalian hyaluronidase; and / or c) a bacterial hyaluronidase; iii) the ECM component is Versican and the ECM degrading polypeptide is: a) chondroitin ABC lyase; b) a microbial chondroitin ABC lyase or a mammalian chondroitin ABC lyase; and / or c) a bacterial chondroitin ABC lyase; iv) the ECM component is Versican and the ECM degrading polypeptide is: a) neuraminidase; b) a microbial neuraminidase or a mammalian neuraminidase; and / or c) a bacterial neuraminidase; v) the ECM component is Versican and the ECM degrading polypeptide is: a) PNGase; b) a microbial PNGase or a mammalian PNGase; and / or c) a bacterial PNGase; vi) the heterologous extracellular matrix (ECM) degrading polypeptide: a) is a hyaluronidase and comprises or consists of an amino acid sequence of SEQ ID NO: 1; is a chondroitin ABC Lyase and comprises or consists of an amino acid sequence of SEQ ID NO: 3 or 47; is a neuraminidase and comprises or consists of an amino acid sequence of SEQ ID NO: 5; or is a PNGase and comprises or consists of an amino acid sequence of SEQ ID NO: 7; or comprises or consists of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, or SEQ ID NO: 47; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%,at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, or SEQ ID NO: 48; vii) the heterologous extracellular matrix (ECM) degrading polypeptide is a bacterial hyaluronidase; and / or viii) the heterologous extracellular matrix (ECM) degrading polypeptide is a bacterial hyaluronidase that: a) comprises or consists of an amino acid sequence of SEQ ID NO: 1; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 2, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO:

2.

6. The recombinant bacterial cell of any one of claims 1, 2, 4 and 5, wherein: i) a) the tumour-inducible promoter is a hypoxia-inducible promoter; b) the tumour-inducible promoter is a hypoxia-inducible promoter selected from the group comprising or consisting of: LOR9, LOR7, LOR1, pflE, pepT, YbiY, and pvhb; or ii) a) the tumour-inducible promoter is a pH inducible promoter; and / or b) the tumour-inducible promoter is a pH inducible promoter selected from the group comprising or consisting of: LPR7, LPR1, LPR9, Stm1787, hyaA, P170-IL, P170-MG, P1, P2, and P3.

7. The recombinant bacterial cell of any one of claims 1, 2, and 4-6, wherein: a) the hypoxia-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, atleast 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; b) the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; c) the pH-inducible promoter comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ IDNO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, or SEQ ID NO: 105; and / or d) the pH-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, or SEQ ID NO: 61; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, or SEQ ID NO: 60, or SEQ ID NO:

61. . The recombinant bacterial cell of any one of claims 1, 2, and 4-7, wherein: a) the tumour-inducible promoter is a pH-inducible and hypoxia-inducible promoter; b) the tumour-inducible promoter is a pH-inducible and hypoxia-inducible promoter that is LOR9; c) the tumour-inducible promoter is a pH-inducible and hypoxia-inducible promoter that is LOR9 and comprises a ribosome binding site (RBS) encoded by a nucleotide sequence of SEQ ID NO: 73, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 73; and / or b) the tumour-inducible promoter is a pH-inducible and hypoxia-inducible promoter that is LOR9 and is encoded by a nucleotide sequence of SEQ ID NO: 55 or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO:

55.

9. The recombinant bacterial cell of claims 1, 2, and 4-8, wherein the tumour-inducible promoter is a hypoxia-inducible promoter that: i) is activated and drives expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) between about 0% and about 2%, about 0.2% and about 1.8%, about 0.4% and about 1.6%, about 0.6% and about 1.4%, about 0.8% and about 1.2%, about 0% and about 1%, about 0.2% and about 0.8%, about 0.4 and about 0.6%, 1% and 2%, about 1.2% and about 1.8%, about 1.4% and about 1.6%;b) between 0% and 2%, 0.2% and 1.8%, 0.4% and 1.6%, 0.6% and 1.4%, 0.8% and 1.2%, 0% and 1%, 0.2% and 0.8%, 0.4 and 0.6%, 1% and 2%, 1.2% and 1.8%, 1.4% and 1.6%; c) below about 2%, below about 1.5%, below about 1.6%, below about 1.4%, below about 1.2%, below about 1%, below about 0.8%, below about 0.6%, below about 0.4%, below about 0.2% or lower; d) below 2%, below 1.5%, below 1.6%, below 1.4%, below 1.2%, below 1%, below 0.8%, below 0.6%, below 0.4%, below 0.2% or lower; e) about 2%, about 1.8%, about 1.6%, about 1.4%, about 1.2%, about 1%, about 0.8%, about 0.6%, about 0.4%, about 0.2%; and / or f) 2%, 1.8%, 1.6%, 1.4%, 1.2%, 1%, 0.8%, 0.6%, 0.4%, 0.2%; ii) is not activated and does not drive expression of the heterologous ECM degrading polypeptide in normoxia; and / or iii) is not activated and does not drive expression of the heterologous ECM degrading polypeptide in normoxia and is not activated and does not drive expression of the heterologous ECM degrading polypeptide at an oxygen concentration of: a) above about 6%, above about 5%, above about 4%, or above about 3%; b) above 6%, above 5%, above 4%, or above 3%; c) about 6%, about 5%, about 4%, about 3%; and / or d) 6%, 5%, 4%, 3%.

10. The recombinant bacterial cell of any one of claims 1, 2, and 4-9, wherein: i) the tumour-inducible promoter is a pH-inducible promoter that is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH; ii) the tumour-inducible promoter is a pH-inducible promoter that is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH that is is: a) between about pH 5.5 and about pH 7, about pH 5.6 and about pH 6.9, about pH 5.7 and about pH 6.8, about pH 5.8 and about pH 6.7, about pH 5.9 and about pH 6.6, about pH 6.0 and about pH 6.5, about pH 6.1 and about pH 6.4, about pH 6.2 and about pH 6.3; b) between pH 5.5 and pH 7, pH 5.6 and pH 6.9, pH 5.7 and pH 6.8, pH 5.8 and pH 6.7, pH 5.9 and pH 6.6, pH 6.0 and pH 6.5, pH 6.1 and pH 6.4, pH 6.2 and pH 6.3c) below about pH 7, below about pH 6.9, below about pH 6.8, below about pH 6.7, below about pH 6.6, below about pH 6.5, below about pH 6.4, below about pH 6.3, below about pH 6.2, below about pH 6.1, below about pH 6.0, below about pH 5.9, below about pH 5.8, below about pH 5.7, below about pH 5.6, or lower; d) below pH 7, below pH 6.9, below pH 6.8, below pH 6.7, below pH 6.6, below pH 6.5, below pH 6.4, below pH 6.3, below pH 6.2, below pH 6.1, below pH 6.0, below pH 5.9, below pH 5.8, below pH 5.7, below pH 5.6; e) about pH 5.5, about pH 5.6, about pH 5.7, about pH 5.8, about pH 5.9, about pH 6.0, about pH 6.1, about pH 6.2, about pH 6.3, about pH6.4, about pH 6.5, about pH 6.6, about pH 6.7, about pH 6.8, about pH 6.9, or about pH 7; and / or f) pH 5.5, pH 5.6, pH 5.7, pH 5.8, pH 5.9, pH 6.0, pH 6.1, pH 6.2, pH 6.3, pH6.4, pH 6.5, pH 6.6, pH 6.7, pH 6.8, pH 6.9, or pH 7; and / or iii) the tumour-inducible promoter is a pH-inducible promoter that is activated and drives expression of the heterologous ECM degrading polypeptide at an acidic pH that is: a) between about pH 5.9 and about pH 6.5, about pH 5.95 and about pH 6.45, about pH 6.0 and about pH 6.4, about pH 6.05 and about pH 6.35, about pH 6.1 and about 6.3, or about pH 6.15 and about pH 6.25; b) between pH 5.9 and pH 6.5, pH 5.95 and pH 6.45, pH 6.0 and pH 6.4, pH 6.05 and pH 6.35, pH 6.1 and 6.3, or pH 6.15 and pH 6.25; c) about pH 5.9, about pH 5.95, about pH 6.0, about pH 6.05, about pH 6.1, about pH 6.15, about pH 6.2, about pH 6.25, about pH 6.3, about pH 6.35, about pH 6.4, about pH 6.45, or about pH 6.5; and / or d) pH 5.9, pH 5.95, pH 6.0, pH 6.05, pH 6.1, pH 6.15, pH 6.2, pH 6.25, pH 6.3, pH 6.35, pH 6.4, pH 6.45, or pH 6.

5.

11. The recombinant bacterial cell of any of claims 1, 2, and 4-10, wherein: a) the tumour-inducible promoter is a hypoxia-inducible promoter that comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding sequence; a modified operator sequence; or any combination thereof; or b) the tumour-inducible promoter is a pH-inducible promoter comprises a modified regulatory element selected from the group comprising or consisting of: a modified RNA polymerase binding sequence; a modified operator sequence; or any combination thereof.

12. The recombinant bacterial cell of any one of claims 1-11, wherein the heterologous extracellular matrix (ECM) degrading polypeptide is a fusion polypeptide comprising an ECM degrading domain and: a) a secretion domain; b) two secretion domains; c) a cleavage domain; and / or d) a cleavage domain that is positioned between the ECM degrading domain and the secretion domain.

13. The recombinant bacterial cell of claim 12, wherein: i) the secretion domain is selected from the group comprising or consisting of: a PelB secretion signal sequence, a YebF carrier protein, a CtxB signal sequence, an AIDA-I autotransporter, a FliC signal sequence, and a Usp45 signal sequence, or any combination thereof; ii) the secretion domain: a) comprises or consists of an amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36; iii) the cleavage domain comprises a matrix metalloprotease (MMP) cleavage site, optionally wherein the cleavage domain: a) comprises or consists of an amino acid sequence of SEQ ID NO: 116; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 116; and / orb) is encoded by a nucleotide sequence of SEQ ID NO: 117, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 117; and / or iv) the fusion polypeptide: a) comprises an ECM degrading domain that comprises a hyaluronidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46; or b) comprises an ECM degrading domain that comprises a neuraminidase, and: i) comprises or consists of an amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 114or an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5, SEQ ID NO: 106, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 112, or SEQ ID NO: 114; and / or ii) is encoded by a nucleotide sequence of SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 115, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113, or SEQ ID NO: 115.

14. The recombinant bacterial cell of any of claims 1-13, wherein the nucleic acid further comprises a nucleotide sequence encoding a transcriptional regulatory polypeptide.

15. The recombinant bacterial cell of claim 14, wherein where the secretion domain is a FliC signal sequence, the transcriptional regulatory peptide is selected from the group comprising or consisting of: a FliC repressor; optionally wherein the FliC repressor is a GadE repressor.

16. The recombinant bacterial cell of claim 15, wherein the transcriptional regulatory peptide: a) comprises or consists of an amino acid sequence of SEQ ID NO: 49; or of an amino acid sequence at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 49; and / or b) is encoded by a nucleotide sequence of SEQ ID NO: 50, or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO:

50.

17. The recombinant bacterial cell of any of claims 1-16, wherein: i) the cell is a non-pathogenic bacterial cell, a commensal cell, or a probiotic cell; ii) the cell is a facultatively anaerobic cell; and / or iii) the cell is: a) a gram-negative bacterial cell; optionally wherein the gram-negative bacterial cell is selected from the group comprising or consisting of: an Escherichia coli cell; optionally wherein the gram-negative bacterial cell is an Escherichia coli K12 cell; optionally wherein the Escherichia coli K12 cell is Escherichia coli K12 MG1655 cell; or b) a gram-positive bacterial cell; optionally wherein the gram-positive bacterial cell is a lactic acid bacterial cell; optionally wherein the lactic acid bacterial cell is selected from the groupcomprising or consisting of: a Lactococcus lactis cell, a Lactobacillus cell, and a Bifidobacterium cell optionally wherein the gram-positive bacterial cell is a Lactococcus lactis MG1363 cell.

18. The recombinant bacterial cell of any of claims 1-17, wherein: a) the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC); b) the nucleic acid is a plasmid; or c) the nucleic acid integrated into the genome of the cell.

19. The recombinant bacterial cell of any of claims 1-18, wherein the cell is capable of accumulating in a target tissue or tumour.

20. A hypoxia-inducible promoter, wherein the hypoxia-inducible promoter is a promoter according to any of claims 6-19.

21. The hypoxia-inducible promoter of claim 20, wherein the hypoxia-inducible promoter is an engineered hypoxia-inducible promoter.

22. The hypoxia-inducible promoter of claim 20 or 21, wherein: a) the hypoxia-inducible promoter is an LOR9, an LOR7 promoter, or an LOR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO:

56.

23. A pH-inducible promoter, wherein the pH-inducible promoter is a promoter according to any of claims 6-19.

24. The pH-inducible promoter of claim 23, wherein the pH-inducible promoter is an engineered pH-inducible promoter.

25. The pH-inducible promoter of claim 23 or 24, wherein:a) the pH-inducible promoter is an LPR9, an LPR7 promoter, or an LPR1 promoter; and / or b) wherein the hypoxia-inducible promoter is encoded by a nucleotide sequence of SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO: 59; or a nucleotide sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 57, SEQ ID NO: 58, or SEQ ID NO:

59.

26. A nucleic acid comprising a nucleotide sequence of the hypoxia-inducible promoter of any one of claims 20-22 and / or the pH-inducible promoter of any one of claim 23-25.

27. A nucleic acid comprising a nucleotide sequence encoding an extracellular matrix (ECM) degrading polypeptide.

28. The nucleic acid of claim 27: i) wherein the extracellular matrix (ECM) degrading polypeptide is the heterologous extracellular matrix (ECM) degrading polypeptide according to any of claims 1-19; ii) wherein the nucleic acid further comprises a promoter; iii) wherein the nucleic acid further comprises a promoter that is the promoter of any of claims 1, 2, and 4-26; iv) wherein the nucleic acid further comprises a promoter, wherein the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the promoter; v) further comprising a transcriptional regulatory element; optionally wherein the transcriptional regulatory element is the transcriptional regulatory element selected from the group comprising or consisting of: a terminator sequence, a repressor binding sequence, an insulator, an operator sequence, or any combination thereof; vi) further comprising a transcriptional regulatory element; optionally wherein the transcriptional regulatory element is the transcriptional regulatory element selected from the group comprising or consisting of: a terminator sequence, a repressor binding sequence, an insulator, an operator sequence, or any combination thereof, wherein the nucleotide sequence encoding the extracellular matrix (ECM) degrading polypeptide is operably linked to the transcriptional regulatory element; and / or vii) the nucleic acid is selected from the group comprising or consisting of: a plasmid, a phagemid, and a bacterial artificial chromosome (BAC);viii) wherein the nucleic acid is a plasmid.

29. A cell comprising the engineered hypoxia-inducible promoter of any one of claims 20-22, the engineered pH-inducible promoter of any one of claims 23-25, and / or the nucleic acid of any one of claims 26-28.

30. The cell of claim 29, wherein the cell is a recombinant bacterial cell; optionally wherein the cell is a recombinant bacterial cell according to any of claims 1-19.

31. The recombinant bacterial cell of any of claims 1-19 or cell of claim 29 or 30 for use in medicine.

32. The recombinant bacterial cell of any of claims 1-19 or cell of claim 29 or 30 for use in treating cancer.

33. The recombinant bacterial cell for use of any of claims 31-32, wherein the use comprises administering an effective dose of the cell to a subject with cancer.

34. The recombinant bacterial cell or the cell for use of any of claims 29-33, wherein: i) the cancer is a tumour solid cancer, optionally wherein the cancer is an immune-excluded solid tumour cancer and / or an immune-excluded tumour; ii) the cancer is a cancer that comprises extracellular matrix; iii) the cancer is a cancer that comprises extracellular matrix and is selected from the group comprising or consisting of: triple-negative breast cancer, microsatellite stable colon cancer, and pancreatic cancer; and / or iv) the cancer is not a cancer that does not comprise extracellular matrix; v) the cancer is not a cancer that does not comprise extracellular matrix and is not a blood cancer; vi) the cancer is not a cancer that does not comprise extracellular matrix, is not a blood cancer, and is not a cancer selected from the group comprising or consisting of: leukaemia, myeloma, and lymphoma; and / or vii) the recombinant bacterial cell or cell is: a) administered prior to or subsequent to administration of a cancer therapeutic; b) co-administered with a cancer therapeutic; c) co-administered with a cancer therapeutic, wherein the cancer therapeutic is selected from the group comprising or consisting of: an antibody (optionally selected from the group comprising or consisting of: animmune checkpoint inhibitor (ICI), T-cell engager, and a bispecific antibody or an antibody-drug conjugate), a cell therapy (optionally selected from the group comprising or consisting of: a T-cell, a CAR-T cell, and a T4 cell), a chemotherapy agent (optionally selected from the group comprising or consisting of: FOLFOX, Gemcitabine, Paclitaxel, Cisplatin, Epirubicin and Irinotecan) an Immunomodulator (optionally selected from the group comprising or consisting of: a cytokine and a chemokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), and a second live biotherapeutic (optionally selected from the group comprising or consisting of: an engineered live biotherapeutic and a recombinant bacterial cell); or d) co-administered with a cancer therapeutic, wherein the cancer therapeutic is selected from the group comprising or consisting of: an antibody (optionally an immune checkpoint inhibitor antibody, bispecific antibody or an antibody-drug conjugate), a hormonal therapy, a targeted therapy, an immunotherapy, a cell therapy (optionally a tumour infiltrating lymphocyte (TIL), a lymphocyte with an engineered T cell receptor (TCR), a CAR T cell, or a Natural Killer cell), an immunomodulator (optionally a chemokine or a cytokine), a vaccine (optionally an mRNA vaccine), a virus (optionally an oncolytic virus), another live biotherapeutic (optionally an engineered live biotherapeutic), a chemotherapy (optionally an alkylating agent (optionally temozolomide and carboplatin), an anti-metabolite (optionally 5-FU or gemcitabine), an anti-tumour antibiotic (optionally doxorubicin), a topoisomerase inhibitor (optionally irinotecan), a mitotic inhibitor (optionally a taxane, optionally paclitaxel or docetaxel), a corticosteroid (optionally dexamethasone).

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