Link to Pubmed [PMID] – 31032549
Environ. Microbiol. 2019 Apr;
Clostridium difficile is the main cause of antibiotic-associated diarrhoea. Inside the gut, C. difficile must adapt to the stresses it copes with, by inducing protection, detoxification and repair systems that belong to the general stress response involving σ . Following stresses, σ activation requires a PP2C phosphatase to dephosphorylate the anti-anti-sigma factor RsbV that allows its interaction with the anti-sigma factor RsbW and the release of σ . In this work, we studied the signalling pathway responsible for the activation of σ in C. difficile. Contrary to other firmicutes, the expression of sigB in C. difficile is constitutive and not autoregulated. We confirmed the partner switching mechanism that involved RsbV, RsbW and σ . We also showed that CD2685, renamed RsbZ, and its phosphatase activity are required for RsbV dephosphorylation triggering σ activation. While CD0007 and CD0008, whose genes belong to the sigB operon, are not involved in σ activity, depletion of the essential iron-sulphur flavoprotein, CD2684, whose gene forms an operon with rsbZ, prevents σ activation. Finally, we observed that σ is heterogeneously active in a subpopulation of C. difficile cells from the exponential phase, likely leading to a ‘bet-hedging’ strategy allowing a better chance for the cells to survive adverse conditions.