The Vibrio cholerae quorum-sensing protein VqmA integrates cell density, environmental, and host-derived cues into the control of virulence

Abstract

Scientific AbstractQuorum sensing is a chemical communication process in which bacteria use the production, release, and detection of signal molecules called autoinducers to orchestrate collective behaviors. The human pathogen Vibrio cholerae requires quorum sensing to infect the small intestine. There, V. cholerae encounters the absence of oxygen and the presence of bile. We show that these two stimuli differentially affect quorum sensing function and, in turn, V. cholerae pathogenicity. The quorum-sensing receptor-transcription factor called VqmA, that detects the autoinducer called DPO, also detects the lack of oxygen and the presence of bile. Detection occurs via DPO-, oxygen-, bile-, and redox-responsive disulfide bonds that alter VqmA DNA binding activity. We propose that VqmA serves as an information processing hub that integrates quorum- sensing information, redox status, the presence or absence of oxygen, and host cues. In response to the information acquired through this mechanism, V. cholerae appropriately modulates its virulence output. Lay AbstractQuorum sensing (QS) is a process of chemical communication bacteria use to orchestrate collective behaviors. QS communication relies on chemical signal molecules called autoinducers. QS regulates virulence in Vibrio cholerae, the causative agent of the disease cholera. Transit into the human small intestine, the site of cholera infection, exposes V. cholerae to the host environment. In this study, we show that the combination of two stimuli encountered in the small intestine, the absence of oxygen and the presence of host-produced bile, impinge on V. cholerae QS function and, in turn, pathogenicity. We suggest that possessing a QS system that is responsive to multiple environmental, host, and cell density cues enables V. cholerae to fine-tune its virulence capacity in the human intestine.