title: Differential Thiol-Based Switches Jump-Start Vibrio cholerae Pathogenesis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nawar
authors.initials: N
authors.lastname: Naseer
authors.affiliation: College of Life Sciences, Huanggang Normal University, Huanggang 438000, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Xiang
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Kan
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Goulian
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: junzhu@mail.med.upenn.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014734:Vibrio cholerae / Q000378:metabolism* / Q000821:virology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors