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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
Clostridium difficile toxin synthesis is negatively regulated by TcdC.
B Dupuy1, R Govind1, A Antunes1
1Unité des Toxines et Pathogénie Bactérienne, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
Journal of Medical Microbiology
|May 16, 2008
Summary
Clostridium difficile toxin production is regulated by TcdC, a negative regulator. Mutations in tcdC are linked to hypertoxigenicity in epidemic strains, highlighting its role in C. difficile pathogenesis.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Clostridium difficile toxin synthesis is regulated by growth phase and environmental signals.
- Toxin genes (tcdA, tcdB) are in a pathogenicity locus with accessory genes (tcdR, tcdC, tcdE).
- TcdR acts as an alternative sigma factor, positively regulating toxin and its own gene transcription.
Purpose of the Study:
- To investigate the role of TcdC in regulating Clostridium difficile toxin synthesis.
- To elucidate the mechanism by which TcdC negatively regulates toxin gene expression.
- To explore the association between tcdC mutations and hypertoxigenicity in epidemic strains.
Main Methods:
- Genetic analysis of tcdC and its role in toxin regulation.
- Biochemical assays to determine TcdC's interaction with TcdR-RNA polymerase complex.
- Analysis of tcdC mutations in Clostridium difficile NAP1/027 epidemic strains.
Main Results:
- TcdC is expressed during exponential phase, suggesting a negative regulatory role.
- TcdC negatively regulates toxin synthesis by inhibiting TcdR-RNA polymerase binding to tcdA and tcdB promoters.
- Epidemic Clostridium difficile strains (NAP1/027) exhibit mutations in tcdC, correlating with hypertoxigenicity.
- A frameshift mutation in tcdC is implicated in the hypervirulence of epidemic strains.
Conclusions:
- TcdC is a critical negative regulator of Clostridium difficile toxin production.
- TcdC functions by interfering with the transcriptional machinery of toxin genes.
- Mutations in tcdC, particularly frameshift mutations, contribute to the increased virulence of epidemic Clostridium difficile strains.
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