Differential Thiol-Based Switches Jump-Start Vibrio cholerae Pathogenesis

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.