Abstract
Summary The alternative sigma factor σ B is the master regulator of the general stress regulon that comprises approximately 200 genes whose products confer a comprehensive stress resistance to Bacillus subtilis . The characterization of MgsR ( m odulator of the g eneral s tress r esponse) revealed that the activation and induction of σ B are a prerequisite but not sufficient for a full expression of all general stress genes. MgsR is a paralogue of the global regulator of the diamide stress response, Spx, and controls a subregulon of the general stress response. Here we demonstrate that MgsR activity is controlled at multiple levels. These mechanisms include a positive autoregulatory loop on mgsR transcription, a post‐translational redox‐sensitive activation step by an intramolecular disulfide bond formation in response to ethanol stress in vivo , as well as rapid proteolytic degradation of MgsR by the ClpXP and ClpCP proteases. Our results indicate an elaborate regulatory network integrating secondary oxidative stress signals into a σ B ‐mediated regulatory cascade that is aimed at rapid and finely tuned target gene expression to coordinately fulfil the physiological needs of the cell in the face of multiple environmental changes.