MsrR is a thiol-based oxidation-sensing regulator of the XRE family that modulates C. glutamicum oxidative stress resistance

Background Corynebacterium glutamicum thrives under oxidative stress caused by the inevitably extreme environment during fermentation as it harbors antioxidative stress genes. Antioxidant genes are controlled by pathway-specific sensors that act in response to growth conditions. Although many families of oxidation-sensing regulators in C. glutamicum have been well described, members of the xenobiotic-response element (XRE) family, involved in oxidative stress, remain elusive. Results In this study, we report a novel redox-sensitive member of the XER family, MsrR (multiple stress resistance regulator). MsrR is encoded as part of the msrR - 3-mst (3-mercaptopyruvate sulfurtransferase) operon; msrR - 3-mst is divergent from multidrug efflux protein MFS . MsrR was demonstrated to bind to the intergenic region between msrR - 3-mst and mfs . This binding was prevented by an MsrR oxidation-mediated increase in MsrR dimerization. MsrR was shown to use Cys62 oxidation to sense oxidative stress, resulting in its dissociation from the promoter. Elevated expression of msrR - 3-mst and mfs was observed under stress. Furthermore, a Δ msrR mutant strain displayed significantly enhanced growth, while the growth of strains lacking either 3-mst or mfs was significantly inhibited under stress. Conclusion This report is the first to demonstrate the critical role of MsrR-3-MST-MFS in bacterial stress resistance.