Development of Clostridium difficile R20291ΔPaLoc model strains and in vitro methodologies reveals CdtR is required for the production of CDT to cytotoxic levels

Lessa, 2015, Burden of Clostridium difficile infection in the United States, N. Engl. J. Med., 372, 825, 10.1056/NEJMoa1408913 Vedantam, 2012, Clostridium difficile infection: toxins and non-toxin virulence factors, and their contributions to disease establishment and host response, Gut Microbes, 3, 121, 10.4161/gmic.19399 O'Connor, 2009, Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain, Gastroenterology, 136, 1913, 10.1053/j.gastro.2009.02.073 Carman, 2011, Clostridium difficile binary toxin (CDT) and diarrhea, Anaerobe, 17, 161, 10.1016/j.anaerobe.2011.02.005 Carter, 2007, Binary toxin production in Clostridium difficile is regulated by CdtR, a LytTR family response regulator, J. Bacteriol., 189, 7290, 10.1128/JB.00731-07 Ng, 2013, Expanding the repertoire of gene tools for precise manipulation of the Clostridium difficile genome: allelic exchange using pyrE alleles, PLoS One, 8, e56051, 10.1371/journal.pone.0056051 Heap, 2012, Integration of DNA into bacterial chromosomes from plasmids without a counter-selection marker, Nucleic Acids Res., 40, e59, 10.1093/nar/gkr1321 Lyon, 2016, CdtR regulates TcdA and TcdB production in Clostridium difficile, PLoS Pathog., 12, e1005758, 10.1371/journal.ppat.1005758 Voth, 2005, Clostridium difficile toxins: mechanism of action and role in disease, Clin. Microbiol. Rev., 18, 247, 10.1128/CMR.18.2.247-263.2005 Gerding, 2014, Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance, Gut Microbes, 5, 15, 10.4161/gmic.26854 Fernie, 1984, Rabbit enterotoxaemia: purification and preliminary characterisation of a toxin produced by Clostridium spiroforme, FEMS Microbiol. Lett., 21, 207, 10.1111/j.1574-6968.1984.tb00212.x Perelle, 1997, Production of a complete binary toxin (actin-specific ADP-ribosyltransferase) by Clostridium difficile CD196, Infect. Immun., 65, 1402, 10.1128/iai.65.4.1402-1407.1997