Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Nanjing Agricultural University, Nanjing 210095, China.
Cell Rep. 2016 Jan 12;14(2):347-54. doi: 10.1016/j.celrep.2015.12.038. Epub 2015 Dec 31.
Bacterial pathogens utilize gene expression versatility to adapt to environmental changes. Vibrio cholerae, the causative agent of cholera, encounters redox-potential changes when it transitions from oxygen-rich aquatic reservoirs to the oxygen-limiting human gastrointestinal tract. We previously showed that the virulence regulator AphB uses thiol-based switches to sense the anoxic host environment and transcriptionally activate the key virulence activator tcpP. Here, by performing a high-throughput transposon sequencing screen in vivo, we identified OhrR as another regulator that enables V. cholerae rapid anoxic adaptation. Like AphB, reduced OhrR binds to and regulates the tcpP promoter. OhrR and AphB displayed differential dynamics in response to redox-potential changes: OhrR is reduced more rapidly than AphB. Furthermore, OhrR thiol modification is required for rapid activation of virulence and successful colonization. This reveals a mechanism whereby bacterial pathogens employ posttranslational modifications of multiple transcription factors to sense and adapt to dynamic environmental changes.
细菌病原体利用基因表达的多功能性来适应环境变化。霍乱弧菌是霍乱的病原体，当它从富含氧气的水生储层过渡到氧气有限的人类胃肠道时，会经历氧化还原电位的变化。我们之前曾表明，毒力调节因子 AphB 使用基于巯基的开关来感知缺氧的宿主环境，并转录激活关键的毒力激活剂 tcpP。在这里，我们通过在体内进行高通量转座子测序筛选，鉴定出 OhrR 是另一个使霍乱弧菌能够快速适应缺氧的调节剂。与 AphB 一样，还原型 OhrR 与 tcpP 启动子结合并调节其活性。OhrR 和 AphB 对氧化还原电位变化的反应表现出不同的动态：OhrR 的还原速度快于 AphB。此外，OhrR 的巯基修饰对于快速激活毒力和成功定植是必需的。这揭示了一种机制，即细菌病原体利用多个转录因子的翻译后修饰来感知和适应动态环境变化。
