Modulation of toxin production by the flagellar regulon in Clostridium difficile

  1. Get@NRC: Modulation of toxin production by the flagellar regulon in Clostridium difficile (Opens in a new window)
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Journal titleInfection and Immunity
Pages35213532; # of pages: 12
Subjectbacterial protein; CD0240 protein; flhB protein; fliC protein; fliF protein; fliM protein; fliR protein; mutant protein; unclassified drug; animal experiment; animal model; article; bacterial genetics; bacterial virulence; Clostridium difficile; controlled study; cytotoxicity; female; flagellum; gene expression; gene inactivation; gene locus; gene regulatory network; genetic transcription; immunoassay; immunoblotting; nonhuman; priority journal; protein secretion; proteomics; regulon; supernatant; toxin synthesis; Animals; Bacterial Proteins; Bacterial Toxins; Clostridium difficile; Cricetinae; Enzyme-Linked Immunosorbent Assay; Female; Flagella; Gene Expression Regulation, Bacterial; Mutation; Proteomics; RNA, Bacterial; Sigma Factor; Transcriptome
AbstractWe show in this study that toxin production in Clostridium difficile is altered in cells which can no longer form flagellar filaments. The impact of inactivation of fliC, CD0240, fliF, fliG, fliM, and flhB-fliR flagellar genes upon toxin levels in culture supernatants was assessed using cell-based cytotoxicity assay, proteomics, immunoassay, and immunoblotting approaches. Each of these showed that toxin levels in supernatants were significantly increased in a fliC mutant compared to that in the C. difficile 630 parent strain. In contrast, the toxin levels in supernatants secreted from other flagellar mutants were significantly reduced compared with that in the parental C. difficile 630 strain. Transcriptional analysis of the pathogenicity locus genes (tcdR, tcdB, tcdE, and tcdA) revealed a significant increase of all four genes in the fliC mutant strain, while transcription of all four genes was significantly reduced in fliM, fliF, fliG, and flhB-fliR mutants. These results demonstrate that toxin transcription in C. difficile is modulated by the flagellar regulon. More significantly, mutant strains showed a corresponding change in virulence compared to the 630 parent strain when tested in a hamster model of C. difficile infection. This is the first demonstration of differential flagellum-related transcriptional regulation of toxin production in C. difficile and provides evidence for elaborate regulatory networks for virulence genes in C. difficile. © 2012, American Society for Microbiology.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269342
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Record identifier211e9e90-c722-49aa-a9e7-58ebfe9fe2f2
Record created2013-12-12
Record modified2016-05-09
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