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论文题目：c-di-GMP inhibitsthe DNA bindingactivity ofH-NS in Salmonella
论文作者：Shuyu Li, Qinmeng Liu, Chongyi Duan, Jialin Li, Hengxi Sun, Lei Xu, Qiao Yang, Yao Wang,Xihui Shen*,Lei Zhang*
论文摘要：Cyclic di-GMP (c-di-GMP) is a second messenger that transduces extracellular stimuli into cellular responses and regulates various biological processes in bacteria. H-NS is a global regulatory protein that represses expression of many genes, but how H-NS activity is modulated by environmental signals remains largely unclear. Here, we show that high intracellular c-di-GMP levels, induced by environmental cues, relieve H-NS-mediated transcriptional silencing in Salmonella enterica serovar Typhimurium. We find that c-di-GMP binds to the H-NS protein to inhibit its binding to DNA, thus derepressing genes silenced by H-NS. However, c-di-GMP is unable to displace H-NS from DNA. In addition, a K107A mutation in H-NS abolishes response to c-di-GMP but leaves its DNA binding activity unaffected in vivo. Our results thus suggest a mechanism by which H-NS acts as an environment-sensing regulator in Gram-negative bacteria.
c-di-GMP是细菌中广泛存在的一类核苷类第二信使，能够响应外界环境和宿主信号足球竞彩投注截止时间细菌的众多生理和病理过程。组蛋白样类核结构蛋白H-NS是广泛分布于革兰氏阴性细菌中的一类全局性转录足球竞彩投注截止时间因子，参与足球竞彩投注截止时间数百个毒力、代谢、环境应激反应等相关基因的表达。本研究首先发现胆汁酸盐通过c-di-GMP信号途径激活沙门氏菌VI型分泌系统(T6SS)的活性，并以此为切入点，筛选鉴定出抑制T6SS基因表达的H-NS为c-di-GMP的作用靶点。进一步研究表明，c-di-GMP与H-NS结合后，封闭了H-NS的部分DNA结合位点，导致H-NS无法结合DNA，从而解除H-NS对基因表达的抑制作用。转录组测序结果显示，胞内c-di-GMP水平上升后还能减轻H-NS对SPI-2、SPI-3、SPI-5等毒力基因表达的抑制。本研究揭示了H-NS响应外界信号足球竞彩投注截止时间基因表达的一种新模式，丰富了对c-di-GMP信号受体感应及足球竞彩投注截止时间机制的认知，同时为抗细菌感染药物研发提供了新靶点。