College of Life Sciences, Qufu Normal University, Qufu, 273165, Shandong, China.
College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, 466001, Henan, China.
Microb Cell Fact. 2020 Oct 2;19(1):189. doi: 10.1186/s12934-020-01444-8.
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.
谷氨酸棒杆菌在发酵过程中不可避免地处于极端环境下，会受到氧化应激的影响，但它却拥有抗氧化应激基因，因此能够茁壮成长。抗氧化基因受特定途径传感器的控制，这些传感器会根据生长条件做出反应。虽然谷氨酸棒杆菌中许多氧化感应调控因子家族已得到很好的描述，但参与氧化应激的外源响应元件（XRE）家族成员仍难以捉摸。
在本研究中，我们报告了一种新型的 XER 家族的氧化还原敏感成员 MsrR（多种应激抗性调节剂）。MsrR 作为 msrR-3-mst（3-巯基丙酮酸硫转移酶）操纵子的一部分进行编码；msrR-3-mst 与多药外排蛋白 MFS 不同源。已经证实 MsrR 与 msrR-3-mst 和 mfs 之间的基因间区域结合。这种结合被 MsrR 氧化介导的 MsrR 二聚体增加所阻止。已经表明 MsrR 利用 Cys62 氧化来感知氧化应激，从而导致其从启动子上解离。在应激条件下观察到 msrR-3-mst 和 mfs 的表达显著上调。此外，与野生型菌株相比，ΔmsrR 突变菌株在应激条件下的生长明显增强，而缺乏 3-mst 或 mfs 的菌株的生长则受到明显抑制。
本报告首次证明了 MsrR-3-MST-MFS 在细菌应激抗性中的关键作用。
