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Expression of Clostridium difficile Toxins A and B and Their Sigma Factor TcdD Is Controlled by Temperature

Abstract : Growth temperature was found to control the expression of toxins A and B in Clostridium difficile VPI 10463, with a maximum at 37 degrees C and low levels at 22 and 42 degrees C in both peptone yeast (PY) and defined media. The up-regulation of toxin A and B mRNA and protein levels upon temperature upshift from 22 to 37 degrees C followed the same kinetics, showing that temperature control occurred at the level of transcription. Experiments with Clostridium perfringens using gusA as a reporter gene demonstrated that both toxin gene promoters were temperature controlled and that their high activity at 37 degrees C was dependent on the alternative sigma factor TcdD. Furthermore, tcdD was found to be autoinduced at 37 degrees C. Glucose down-regulated all these responses in the C. perfringens constructs, similar to its impact on toxin production in C. difficile PY broth cultures. C. difficile proteins induced at 37 degrees C and thus coregulated with the toxins by temperature were demonstrated by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified as enzymes involved in butyric acid production and as electron carriers in oxidation-reduction reactions. The regulation of toxin production in C. difficile by temperature is a novel finding apparently reflecting an adaptation of the expression of its virulence to mammalian hosts.
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Submitted on : Monday, January 20, 2020 - 3:03:23 PM
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S. Karlsson, B. Dupuy, K. Mukherjee, E. Norin, L. Burman, et al.. Expression of Clostridium difficile Toxins A and B and Their Sigma Factor TcdD Is Controlled by Temperature. Infection and Immunity, 2003, 71 (4), pp.1784-1793. ⟨10.1128/iai.71.4.1784-1793.2003⟩. ⟨pasteur-02445950⟩



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