Nanostructured δ-MnO2incorporated with alkali cations (A-δ-MnO2, A = K+and Na+) has been synthesized and evaluated as a cathode material for aqueous sodium-ion batteries.
Corynebacterium glutamicum, an important industrial and model microorganism, inevitably encountered stress environment during fermentative process. Therefore, the ability of C. glutamicum to withstand stress and maintain the cellular redox balance was vital for cell survival and enhancing fermentation efficiency. To robustly survive, C. glutamicum has been equipped with many types of redox sensors. Although cysteine oxidation-based peroxide-sensing regulators have been well described in C. glutamicum, redox sensors involving in multiple environmental stress response remained elusive. Here, we reported an organic peroxide- and antibiotic-sensing MarR (multiple antibiotics resistance regulators)-type regulator, called OasR (organic peroxide- and antibiotic-sensing regulator). The OasR regulator used Cys95 oxidation to sense oxidative stress to form S-mycothiolated monomer or intermolecular disulfide-containing dimer, resulting in its dissociation from the target DNA promoter. Transcriptomics uncovered the strong up-regulation of many multidrug efflux pump genes and organic peroxide stress-involving genes in oasR mutant, consistent with the phenomenon that oasR mutant showed a reduction in sensitivity to antibiotic and organic peroxide. Importantly, the addition of stress-associated ligands such as cumene hydroperoxide and streptomycin induced oasR and multidrug efflux pump protein NCgl1020 expression in vivo. We speculated that cell resistance to antibiotics and organic peroxide correlated with stress response-induced up-regulation of genes expression. Together, the results revealed that OasR was a key MarR-type redox stress-responsive transcriptional repressor, and sensed oxidative stress generated through hydroxyl radical formation to mediate antibiotic resistance in C. glutamicum.
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 ΔmsrR 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.
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