Vibrio cholerae OmpR Contributes to Virulence Repression and Fitness at Alkaline pH

Abstract

Vibrio cholerae is a Gram-negative human pathogen and the causative agent of the life threatening disease cholera. V. cholerae is a natural inhabitant of marine environment which enters humans through the consumption of contaminated food or water. The ability to transition between aquatic ecosystems and the human host is paramount to the pathogenic success of V. cholerae. The transition between these two disparate environments requires the expression of adaptive responses which are most often regulated by two-component regulatory systems such as the EnvZ/OmpR system, which responds to osmolarity and acidic pH in many Gram-negative bacteria. Previous work in our laboratory indicated that V. cholerae OmpR functioned as a virulence regulator through repression of the LysR-family transcriptional regulator aphB; however, the role of OmpR in V. cholerae biology outside of virulence regulation remained unknown. In this work we sought to further investigate the function of OmpR in V. cholerae biology by defining the OmpR regulon through RNA-sequencing. This led to the discovery that V. cholerae ompR was induced at alkaline pH to repress genes involved in acid tolerance and virulence factor production. In addition, OmpR was required for V. cholerae fitness during growth in alkaline conditions. These findings indicate V. cholerae OmpR has evolved the ability to respond to novel signals during pathogenesis which may play a role in the regulation of adaptive responses to aid in the transition between the human gastrointestinal tract and the marine ecosystem.