Abstract
Many bacteria use quorum sensing (QS) to regulate virulence factor production in response to changes in population density. QS is mediated through the production, secretion, and detection of signaling molecules called autoinducers (AIs) to modulate population-wide behavioral changes. Four histidine kinases, LuxPQ, CqsS, CqsR and VpsS, have been identified in Vibrio cholerae as QS receptors to activate virulence gene expression at low cell density. Detection of AIs by these receptors leads to virulence gene repression at high cell density. The redundancy among these receptors is puzzling since any one of the four receptors is sufficient to support colonization of V. cholerae in the host small intestine. It is believed that one of the functions of such circuit architecture is to prevent interference on any single QS receptor. However, it is unclear what natural molecules can interfere V. cholerae QS and in what environment interference is detrimental. We show here mutants expressing only CqsR without the other three QS receptors are defective in colonizing the host large intestine. We identified ethanolamine, a common intestinal metabolite that can function as a chemical source of QS interference. Ethanolamine specifically interacts with the ligand-binding CACHE domain of CqsR and induces a premature QS response in V. cholerae mutants expressing only CqsR without the other three QS receptors. The effect of ethanolamine on QS gene expression and host colonization is abolished by mutations that disrupt CqsR signal sensing. V. cholerae defective in producing ethanolamine is still proficient in QS, therefore, ethanolamine functions only as an external cue for CqsR. Our findings suggest the inhibitory effect of ethanolamine on CqsR could be a possible source of QS interference but is masked by the presence of the other parallel QS pathways, allowing V. cholerae to robustly colonize the host.
Highlights
Quorum sensing (QS) is used by a wide variety of bacteria to coordinate population-wide changes in behaviors in response to cell density [1]
A metabolite commonly found inside the mammalian intestine, modulates the activity of one of the quorum sensing (QS) receptors in Vibrio cholerae, the etiological agent of the disease cholera
Previous studies have shown that both El Tor and classical biotypes colonize the large intestine in mouse models, suggesting that this niche could be relevant for human infections, especially in asymptomatic carriers and some convalescing patients [29, 30]
Summary
Quorum sensing (QS) is used by a wide variety of bacteria to coordinate population-wide changes in behaviors in response to cell density [1]. At low cell-density (LCD), CqsS and LuxPQ function in parallel with two other histidine kinases, called CqsR and VpsS, to phosphorylate LuxO through an intermediate phosphotransfer protein LuxU [10, 12]. Phosphorylated LuxO promotes the transcription of small RNAs Qrr 1–4 which promote the translation of master regulator AphA [13, 14]. Qrr 1–4 repress the translation of transcriptional regulator HapR at LCD [15, 16] (Fig 1). At HCD, when receptors are bound to their cognate signals, kinase activity is inhibited leading to dephosphorylation of LuxO. This prevents the transcription of Qrr 1–4 thereby inhibiting AphA production and promoting HapR translation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
