CdtR Regulates TcdA and TcdB Production in Clostridium difficile

• DOI: 10.1371/journal.ppat.1005758
• Publication Date: 2016-07-14T16:32:59Z
• Authors: Shelley A. Lyon; Melanie L. Hutton; Julian I. Rood; Jackie K. Cheung; Dena Lyras
• Keywords: Pore-forming toxin

Clostridium difficile is a global health burden and the leading cause of antibiotic-associated diarrhoea worldwide, causing severe gastrointestinal disease death. Three well characterised toxins are encoded by this bacterium in two genetic loci, specifically, TcdB (toxin B) TcdA A) Pathogenicity Locus (PaLoc) binary toxin (CDT) genomically distinct CDT locus (CdtLoc). Toxin production controlled regulators specific to each locus. The orphan response regulator, CdtR, within CdtLoc, up-regulates production. Until now there has been no suggestion that CdtR influences since it not carried all PaLoc-containing strains CdtLoc linked genetically PaLoc. Here we show that, addition CDT, regulates but effect strain dependent. Of clinical relevance, increased TcdA, epidemic ribotype 027 human strains, modulating their virulence mouse infection model. Strains traditionally from animal lineages, notably 078 increasingly being isolated humans phenotypic analysis critical for future studies on important pathogen. CdtR-mediated regulation did occur other backgrounds, including strain. finding gene dependent highlights regulatory diversity between C. isolates importance studying diverse lineages clinically relevant strains. Our work provides first evidence common mechanism may act as regulator