National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Nucleic Acids Res. 2018 Aug 21;46(14):7270-7283. doi: 10.1093/nar/gky611.
Cyclic diguanylate monophosphate (c-di-GMP) is a global signaling molecule that modulates diverse cellular processes through its downstream receptors. However, no study has fully clarified the mechanisms by which c-di-GMP organizes functionally divergent regulators to drive the gene expression for coping with environmental stress. Here, we reported that c-di-GMP can integrate two functionally opposite receptor transcription factors, namely, LtmA and HpoR, into a pathway to regulate the antioxidant processes in Mycobacterium smegmatis. In contrast to HpoR, LtmA is an activator that positively regulates the expression of redox gene clusters and the mycobacterial H2O2 resistance. LtmA can physically interact with HpoR. A high level of c-di-GMP stimulates the positive regulation of LtmA and boosts the physical interaction between the two regulators, further enhancing the DNA-binding ability of LtmA and reducing the inhibitory activity of HpoR. Therefore, upon exposure to oxidative stress, c-di-GMP can orchestrate functionally divergent transcription factors to trigger antioxidant defense in mycobacteria. This finding presents a noteworthy example of how a bacterium remodels its transcriptional network via c-di-GMP in response to environmental stress.
环二鸟苷酸（c-di-GMP）是一种全局信号分子，通过其下游受体调节多种细胞过程。然而，尚无研究完全阐明 c-di-GMP 如何组织功能上不同的调节剂，以驱动应对环境压力的基因表达。在这里，我们报道 c-di-GMP 可以将两种功能相反的受体转录因子 LtmA 和 HpoR 整合到一条通路中，以调节耻垢分枝杆菌中的抗氧化过程。与 HpoR 相反，LtmA 是一种正向调节氧化还原基因簇和分枝杆菌 H2O2 抗性的激活物。LtmA 可以与 HpoR 发生物理相互作用。高水平的 c-di-GMP 刺激 LtmA 的正向调节，并增强两个调节剂之间的物理相互作用，进一步增强 LtmA 的 DNA 结合能力，并降低 HpoR 的抑制活性。因此，在暴露于氧化应激时，c-di-GMP 可以协调功能上不同的转录因子，在分枝杆菌中引发抗氧化防御。这一发现为细菌如何通过 c-di-GMP 重塑其转录网络以应对环境压力提供了一个值得注意的范例。
