title: Repression of Clostridium difficile toxin gene expression by CodY.
abstract: CodY, a global regulator of gene expression in low G + C Gram-positive bacteria, was found to repress toxin gene expression in Clostridium difficile. Inactivation of the codY gene resulted in derepression of all five genes of the C. difficile pathogenicity locus during exponential growth and stationary phase. CodY was found to bind with high affinity to a DNA fragment containing the promoter region of the tcdR gene, which encodes a sigma factor that permits RNA polymerase to recognize promoters of the two major toxin genes as well as its own promoter. CodY also bound, but with low affinity, to the toxin gene promoters, suggesting that the regulation of toxin gene expression by CodY occurs primarily through direct control of tcdR gene expression. Binding of CodY to the tcdR promoter region was enhanced in the presence of GTP and branched-chain amino acids, suggesting a link between nutrient limitation and the expression of C. difficile toxin genes.
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Tufts University, Boston, MA, USA.
authors.forename: Sean S
authors.initials: SS
authors.lastname: Dineen
authors.forename: Anuradha C
authors.initials: AC
authors.lastname: Villapakkam
authors.forename: Jared T
authors.initials: JT
authors.lastname: Nordman
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000096:biosynthesis*; D016360:Clostridioides difficile / Q000235:genetics / Q000502:physiology*; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004768:Enterotoxins / Q000096:biosynthesis*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012808:Sigma Factor / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012097:Repressor Proteins; D012808:Sigma Factor; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile