School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
J Biochem. 2024 Jul 1;176(1):43-54. doi: 10.1093/jb/mvae026.
Protection against oxidative stress is a vital defense mechanism for Mycobacterium tuberculosis within the host. However, few transcription factors that control bacterial antioxidant defense are known. Here, we present evidence that SdrR, encoded by the MSMEG_5712 (Ms5712) gene, functions as an oxidative stress response regulator in Mycobacterium smegmatis. SdrR recognizes an 11-bp motif sequence in the operon's upstream regulatory region and negatively regulates the expression of short-chain dehydrogenases/reductases (SDR). Overexpressing sdrR inhibited SDR expression, which rendered the strain oxidative more stress-sensitive. Conversely, sdrR knockout alleviates SDR repression, which increases its oxidative stress tolerance. Thus, SdrR responds to oxidative stress by negatively regulating sdr expression. Therefore, this study elucidated an underlying regulatory mechanism behind mycobacterial oxidative stress adaptation.
抵御氧化应激是结核分枝杆菌在宿主体内的重要防御机制。然而，目前已知的控制细菌抗氧化防御的转录因子却很少。在这里，我们提供的证据表明，编码 MSMEG_5712（Ms5712）基因的 SdrR 在耻垢分枝杆菌中作为一种氧化应激反应调节剂发挥作用。SdrR 识别操纵子上游调控区的 11 个碱基对序列，并负调控短链脱氢酶/还原酶（SDR）的表达。过表达 sdrR 抑制 SDR 的表达，使菌株对氧化应激更敏感。相反，sdrR 敲除减轻了 SDR 的抑制，从而提高了其对氧化应激的耐受性。因此，SdrR 通过负调控 sdr 表达来应对氧化应激。因此，本研究阐明了分枝杆菌氧化应激适应的潜在调控机制。
