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. 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. This report is the first to demonstrate the critical role of MsrR-3-MST-MFS in bacterial stress resistance.

中文翻译：

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MsrR是XRE家族中基于硫醇的氧化敏感调节剂，可调节谷氨酸棒杆菌的氧化应激抗性

谷氨酸棒杆菌具有抗氧化应激基因，因此在发酵过程中不可避免的极端环境引起的氧化应激下会旺盛生长。抗氧化剂基因受响应于生长条件的途径特异性传感器控制。尽管已经很好地描述了谷氨酸棒杆菌中许多氧化感应调节剂家族，但是涉及氧化应激的异种生物反应元件（XRE）家族成员仍然难以捉摸。在这项研究中，我们报告了XER系列的新型氧化还原敏感成员MsrR（多重抗应力调节剂）。MsrR被编码为msrR-3-mst（3-巯基丙酮酸硫转移酶）操纵子的一部分；msrR-3-mst与多药外排蛋白MFS不同。MsrR被证明绑定到msrR-3-mst和mfs之间的基因间区域。MsrR氧化介导的MsrR二聚化增加阻止了这种结合。MsrR被证明使用Cys62氧化来感应氧化应激，导致其与启动子解离。在压力下观察到msrR-3-mst和mfs的表达升高。此外，ΔmsrR突变菌株显示出显着增强的生长，而缺乏3-mst或mfs的菌株的生长在胁迫下被显着抑制。该报告是首次证明MsrR-3-MST-MFS在细菌抗逆性中的关键作用。而缺乏3-mst或mfs的菌株的生长在胁迫下被显着抑制。该报告是首次证明MsrR-3-MST-MFS在细菌抗逆性中的关键作用。而缺乏3-mst或mfs的菌株的生长在胁迫下被显着抑制。该报告是首次证明MsrR-3-MST-MFS在细菌抗逆性中的关键作用。