S. R. Curry and . Clostridium-difficile, Clin Lab Med, vol.37, issue.2, p.7, 2017.

L. M. Napolitano and C. E. Edmiston, Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update

, Antibiotic resistance threats in the United States, 2013.

G. P. Carter, J. I. Rood, and D. Lyras, The role of toxin A and toxin B in Clostridium difficile-associated disease: Past and present perspectives, Gut Microbes, vol.1, issue.1, pp.58-64, 2010.

S. A. Kuehne, S. T. Cartman, J. T. Heap, M. L. Kelly, A. Cockayne et al., The role of toxin A and toxin B in Clostridium difficile infection, Nature, vol.467, issue.7316, pp.711-714, 2010.

S. A. Kuehne, M. M. Collery, M. L. Kelly, S. T. Cartman, A. Cockayne et al., Importance of toxin A, toxin B, and CDT in virulence of an epidemic Clostridium difficile strain, J Infect Dis, vol.209, issue.1, pp.83-89, 2014.

D. Lyras, J. R. O'connor, P. M. Howarth, S. P. Sambol, G. P. Carter et al., Toxin B is essential for virulence of Clostridium difficile, Nature, vol.458, issue.7242, pp.1176-1185, 2009.

L. J. Deakin, C. S. Fagan, R. P. Dawson, L. F. Pickard, D. J. West et al., The Clostridium difficile spo0A gene is a persistence and transmission factor, Infect Immun, vol.80, issue.8, pp.2704-2715, 2012.

B. Dupuy and A. L. Sonenshein, Regulated transcription of Clostridium difficile toxin genes, Mol Microbiol, vol.27, issue.1, pp.107-127, 1998.

N. Mani and B. Dupuy, Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor, Proc Natl Acad Sci, vol.98, issue.10, pp.5844-5853, 2001.

N. Mani, D. Lyras, L. Barroso, P. Howarth, T. Wilkins et al., Environmental response and autoregulation of Clostridium difficile TxeR, a sigma factor for toxin gene expression, J Bacteriol, vol.184, issue.21, pp.5971-5979, 2002.

S. Karlsson, B. Dupuy, K. Mukherjee, E. Norin, L. G. Burman et al., Expression of Clostridium difficile toxins A and B and their sigma factor TcdD is controlled by temperature, Infect Immun, vol.71, issue.4, pp.1784-93, 2003.

A. N. Edwards, K. L. Nawrocki, and S. M. Mcbride, Conserved oligopeptide permeases modulate sporulation initiation in Clostridium difficile, Infect Immun, vol.82, issue.10, pp.4276-91, 2014.

K. L. Nawrocki, A. N. Edwards, N. Daou, L. Bouillaut, and S. M. Mcbride, CodY-Dependent Regulation of Sporulation in Clostridium difficile, J Bacteriol, vol.198, issue.15, pp.2113-2143, 2016.

A. Antunes, E. Camiade, M. Monot, E. Courtois, F. Barbut et al., Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile, Nucleic Acids Res, vol.40, issue.21, pp.10701-10719, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-01370790

A. Antunes, I. Martin-verstraete, and B. Dupuy, CcpA-mediated repression of Clostridium difficile toxin gene expression, Mol Microbiol, vol.79, issue.4, pp.882-99, 2011.

S. S. Dineen, S. M. Mcbride, and A. L. Sonenshein, Integration of metabolism and virulence by Clostridium difficile CodY, J Bacteriol, vol.192, issue.20, pp.5350-62, 2010.

S. S. Dineen, A. C. Villapakkam, J. T. Nordman, and A. L. Sonenshein, Repression of Clostridium difficile toxin gene expression by CodY, Mol Microbiol, vol.66, issue.1, pp.206-225, 2007.

A. N. Edwards, R. Tamayo, and S. M. Mcbride, A novel regulator controls Clostridium difficile sporulation, motility and toxin production, Mol Microbiol, vol.100, issue.6, pp.954-71, 2016.

K. E. Mackin, G. P. Carter, P. Howarth, J. I. Rood, and D. Lyras, Spo0A differentially regulates toxin production in evolutionarily diverse strains of Clostridium difficile, PLoS One, vol.8, issue.11, p.79666, 2013.

L. J. Pettit, H. P. Browne, L. Yu, W. K. Smits, R. P. Fagan et al., Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism, BMC Genomics, vol.15, p.24568651, 2014.

L. Saujet, M. Monot, B. Dupuy, O. Soutourina, and I. Martin-verstraete, The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile, J Bacteriol, vol.193, issue.13, pp.3186-96, 2011.
URL : https://hal.archives-ouvertes.fr/pasteur-01370840

A. Br and R. Tamayo, A genetic switch controls the production of flagella and toxins in Clostridium difficile, PLoS Genet, vol.13, issue.3, p.1006701, 2017.

A. Aubry, G. Hussack, W. Chen, R. Kuolee, S. M. Twine et al., Modulation of toxin production by the flagellar regulon in Clostridium difficile, Infect Immun, vol.80, issue.10, pp.3521-3553, 2012.

I. El-meouche, J. Peltier, M. Monot, O. Soutourina, M. Pestel-caron et al., Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR, PLoS One, vol.8, issue.12, p.83748, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01370779

R. W. Mckee, M. R. Mangalea, E. B. Purcell, E. K. Borchardt, and R. Tamayo, The second messenger cyclic Di-GMP regulates Clostridium difficile toxin production by controlling expression of sigD, J Bacteriol, vol.195, issue.22, pp.5174-85, 2013.

D. Barilla, T. Caramori, and A. Galizzi, Coupling of flagellin gene transcription to flagellar assembly in Bacillus subtilis, J Bacteriol, vol.176, issue.15, pp.4558-64, 1994.

A. Kuroda and J. Sekiguchi, High-level transcription of the major Bacillus subtilis autolysin operon depends on expression of the sigma D gene and is affected by a sin (flaD) mutation, J Bacteriol, vol.175, issue.3, pp.795-801, 1993.

F. Chu, D. B. Kearns, A. Mcloon, Y. Chai, R. Kolter et al., A novel regulatory protein governing biofilm formation in Bacillus subtilis, Mol Microbiol, vol.68, issue.5, p.18430133, 2008.

P. Kodgire, M. Dixit, and K. K. Rao, ScoC and SinR negatively regulate epr by corepression in Bacillus subtilis, J Bacteriol, vol.188, issue.17, pp.6425-6433, 2006.

F. Chu, D. B. Kearns, S. S. Branda, R. Kolter, and R. Losick, Targets of the master regulator of biofilm formation in Bacillus subtilis, Mol Microbiol, vol.59, issue.4, p.16430695, 2006.

N. K. Gaur, K. Cabane, and I. Smith, Structure and expression of the Bacillus subtilis sin operon, J Bacteriol, vol.170, issue.3, pp.1046-53, 1988.

C. A. Voigt, D. M. Wolf, and A. P. Arkin, The Bacillus subtilis sin operon: an evolvable network motif, Genetics, vol.169, issue.3, pp.1187-202, 2005.

G. L. Draughn, B. G. Bobay, S. D. Stowe, A. L. Olson, E. A. Feldmann et al., Solution structures of biofilm-controlling proteins SinI and SinR from Bacillus subtilis reveal details of DNA-binding and regulatory mechanism, The FASEB Journal, vol.31, issue.1, pp.907-909, 2017.

K. J. Pflughoeft, P. Sumby, and T. M. Koehler, Bacillus anthracis sin locus and regulation of secreted proteases, J Bacteriol, vol.193, issue.3, pp.631-640, 2011.

J. R. O'connor, D. Lyras, K. A. Farrow, V. Adams, D. R. Powell et al., Construction and analysis of chromosomal Clostridium difficile mutants, Mol Microbiol, vol.61, issue.5, p.16925561, 2006.

R. A. Stabler, M. He, L. Dawson, M. Martin, E. Valiente et al., Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium, Genome Biol, vol.10, issue.9, p.102, 2009.

Y. Chai, T. Norman, R. Kolter, and R. Losick, An epigenetic switch governing daughter cell separation in Bacillus subtilis, Genes Dev, vol.24, issue.8, pp.754-65, 2010.

Y. Chai, T. Norman, R. Kolter, and R. Losick, Evidence that metabolism and chromosome copy number control mutually exclusive cell fates in Bacillus subtilis, EMBO J, vol.30, issue.7, pp.1402-1415, 2011.

K. A. Fimlaid, J. P. Bond, K. C. Schutz, E. E. Putnam, J. M. Leung et al., Global analysis of the sporulation pathway of Clostridium difficile, PLoS Genet, vol.9, issue.8, p.1003660, 2013.

K. E. Rosenbusch, D. Bakker, E. J. Kuijper, and W. C. Smits, difficile 630Deltaerm Spo0A regulates sporulation, but does not contribute to toxin production, by direct high-affinity binding to target DNA, PLoS One, vol.7, issue.10, p.48608, 2012.

G. Olmedo, E. G. Ninfa, J. Stock, and P. Youngman, Novel mutations that alter the regulation of sporulation in Bacillus subtilis. Evidence that phosphorylation of regulatory protein SpoOA controls the initiation of sporulation, J Mol Biol, vol.215, issue.3, pp.359-72, 1990.

D. Burbulys, K. A. Trach, and J. A. Hoch, Initiation of sporulation in B. subtilis is controlled by a multicomponent phosphorelay, Cell, vol.64, issue.3, pp.545-52, 1991.

M. Jiang, R. Grau, and M. Perego, Differential processing of propeptide inhibitors of Rap phosphatases in Bacillus subtilis, J Bacteriol, vol.182, issue.2, pp.303-313, 2000.

J. R. Ledeaux and A. D. Grossman, Isolation and characterization of kinC, a gene that encodes a sensor kinase homologous to the sporulation sensor kinases KinA and KinB in Bacillus subtilis, J Bacteriol, vol.177, issue.1, pp.166-75, 1995.

M. Perego, S. P. Cole, D. Burbulys, K. Trach, and J. A. Hoch, Characterization of the gene for a protein kinase which phosphorylates the sporulation-regulatory proteins Spo0A and Spo0F of Bacillus subtilis, J Bacteriol, vol.171, issue.11, pp.6187-96, 1989.

K. Trach, D. Burbulys, M. Strauch, J. J. Wu, N. Dhillon et al., Control of the initiation of sporulation in Bacillus subtilis by a phosphorelay, Res Microbiol, vol.142, issue.7-8, pp.815-838, 1991.

S. Underwood, S. Guan, V. Vijayasubhash, S. D. Baines, L. Graham et al., Characterization of the sporulation initiation pathway of Clostridium difficile and its role in toxin production, J Bacteriol, vol.191, issue.23, pp.7296-305, 2009.

M. M. Collery, S. A. Kuehne, S. M. Mcbride, M. L. Kelly, M. Monot et al., What's a SNP between friends: The influence of single nucleotide polymorphisms on virulence and phenotypes of Clostridium difficile strain 630 and derivatives, Virulence, vol.2016, pp.1-15

E. B. Purcell, R. W. Mckee, S. M. Mcbride, C. M. Waters, and R. Tamayo, Cyclic diguanylate inversely regulates motility and aggregation in Clostridium difficile, J Bacteriol, vol.194, issue.13, pp.100-112, 2012.

E. Bordeleau, L. C. Fortier, F. Malouin, and V. Burrus, c-di-GMP turn-over in Clostridium difficile is controlled by a plethora of diguanylate cyclases and phosphodiesterases, PLoS Genet, vol.7, issue.3, p.1002039, 2011.

J. A. Newman, C. Rodrigues, and R. J. Lewis, Molecular basis of the activity of SinR protein, the master regulator of biofilm formation in Bacillus subtilis, J Biol Chem, vol.288, issue.15, pp.10766-78, 2013.

H. J. Bennett, D. M. Pearce, S. Glenn, C. M. Taylor, M. Kuhn et al., Characterization of relA and codY mutants of Listeria monocytogenes: identification of the CodY regulon and its role in virulence, Mol Microbiol, vol.63, issue.5, pp.1453-67, 2007.

A. Chateau, W. Van-schaik, P. Joseph, L. D. Handke, S. M. Mcbride et al., Identification of CodY targets in Bacillus anthracis by genome-wide in vitro binding analysis, J Bacteriol, vol.195, issue.6, pp.1204-1217, 2013.

C. D. Majerczyk, P. M. Dunman, T. T. Luong, C. Y. Lee, M. R. Sadykov et al., Direct targets of CodY in Staphylococcus aureus, J Bacteriol, vol.192, issue.11, p.20363936, 2010.

L. D. Handke, R. P. Shivers, and A. L. Sonenshein, Interaction of Bacillus subtilis CodY with GTP, J Bacteriol, vol.190, issue.3, pp.798-806, 2008.

M. Ratnayake-lecamwasam, P. Serror, K. W. Wong, and A. L. Sonenshein, Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels, Genes Dev, vol.15, issue.9, pp.1093-103, 2001.

A. L. Sonenshein and . Cody, a global regulator of stationary phase and virulence in Gram-positive bacteria, Curr Opin Microbiol, vol.8, issue.2, pp.203-210, 2005.

B. P. Girinathan, S. Braun, A. R. Sirigireddy, J. E. Lopez, and R. Govind, Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo, PLoS One, vol.11, issue.7, p.160107, 2016.

B. P. Girinathan, M. Monot, D. Boyle, K. N. Mcallister, J. A. Sorg et al., Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291. mSphere, vol.2, pp.383-399, 2017.
URL : https://hal.archives-ouvertes.fr/pasteur-01613368

E. B. Purcell, R. W. Mckee, D. S. Courson, E. M. Garrett, S. M. Mcbride et al., A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase, Infect Immun, vol.85, issue.9, 2017.

H. Vlamakis, Y. Chai, P. Beauregard, R. Losick, and R. Kolter, Sticking together: building a biofilm the Bacillus subtilis way, Nat Rev Microbiol, vol.11, issue.3, pp.157-68, 2013.

K. Ireton and G. Nwt, Grossman AD. spo0J is required for normal chromosome segregation as well as the initiation of sporulation in Bacillus subtilis, J Bacteriol, vol.176, issue.17, pp.5320-5329, 1994.

F. C. Pereira, L. Saujet, A. R. Tome, M. Serrano, M. Monot et al., The spore differentiation pathway in the enteric pathogen Clostridium difficile, PLoS Genet, vol.9, issue.10, p.1003782, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01370787

L. Saujet, F. C. Pereira, M. Serrano, O. Soutourina, M. Monot et al., Genome-wide analysis of cell type-specific gene transcription during spore formation in Clostridium difficile, PLoS Genet, vol.9, issue.10, p.1003756, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01370780

B. P. Girinathan, S. E. Braun, and R. Govind, Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to H2O2, Microbiology, vol.160, pp.47-55, 2014.

E. E. Putnam, A. M. Nock, T. D. Lawley, and A. Shen, SpoIVA and SipL are Clostridium difficile spore morphogenetic proteins, J Bacteriol, vol.195, issue.6, pp.1214-1239, 2013.

F. Teng, B. E. Murray, and G. M. Weinstock, Conjugal transfer of plasmid DNA from Escherichia coli to enterococci: a method to make insertion mutations, Plasmid, vol.39, issue.3, pp.182-188, 1998.

J. T. Heap, S. A. Kuehne, M. Ehsaan, S. T. Cartman, C. M. Cooksley et al., The ClosTron: Mutagenesis in Clostridium refined and streamlined, J Microbiol Methods, vol.80, issue.1, pp.49-55, 2010.

R. Govind and B. Dupuy, Secretion of Clostridium difficile toxins A and B requires the holin-like protein TcdE, PLoS Pathog, vol.8, issue.6, p.1002727, 2012.

A. Criscuolo and S. Brisse, AlienTrimmer: a tool to quickly and accurately trim off multiple short contaminant sequences from high-throughput sequencing reads, Genomics, vol.102, issue.5-6, pp.500-506, 2013.

O. A. Soutourina, M. Monot, P. Boudry, L. Saujet, C. Pichon et al., Genome-wide identification of regulatory RNAs in the human pathogen Clostridium difficile, PLoS Genet, vol.9, issue.5, p.1003493, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01370770

R. Govind, L. Fitzwater, and R. Nichols, Observations on the Role of TcdE Isoforms in Clostridium difficile Toxin Secretion, J Bacteriol, vol.197, issue.15, pp.2600-2609, 2015.

P. Sheffield, S. Garrard, and Z. Derewenda, Overcoming expression and purification problems of RhoGDI using a family of "parallel" expression vectors, Protein Expr Purif, vol.15, issue.1, pp.34-43, 1999.

S. P. Sambol, J. K. Tang, M. M. Merrigan, S. Johnson, and D. N. Gerding, Infection of hamsters with epidemiologically important strains of Clostridium difficile, J Infect Dis, vol.183, issue.12, pp.1760-1766, 2001.