Parallel quorum-sensing system in Vibrio cholerae prevents signal interference inside the host

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.

The quorum-sensing systems of Vibrio campbellii DS40M4 and BB120 are genetically and functionally distinct

“…CqsR and VpsS are additional histidine sensor kinases in V. cholerae that phosphorylate LuxU (36). The ligands for these receptors are unknown (37). BB120 encodes homologs to both V. cholerae CqsR and VpsS with a percent identity of 54.76% and 50.35%, respectively (Table 2).…”

Virulence Regulation and Innate Host Response in the Pathogenicity of Vibrio cholerae

“…Histidine kinases (LuxPQ, CqsS, CqsR, and VpsS) have been identified as QS receptors that initiate virulence gene expression when the cell numbers are less (LCD, Figure 6 ). Any one of the receptors is sufficient for colonization of V. cholerae in the host small intestine (Watve et al, 2020 ). Detection of AIs by these receptors leads to virulence gene repression when the cell numbers are high.…”

Pathogenicity and virulence regulation of Vibrio cholerae at the interface of host-gut microbiome interactions

“…One mechanism of interaction between commensal microbes and V. cholerae pathogenesis is the production of cross-species autoinducers. V. cholerae responds to a set of species-specific (CAI-1) and potentially cross-species (AI-2, DPO, ethanolamine) signals in gene regulation [144,149,181]. The human commensal B. obeum has been shown to upregulate production of an AI-2 molecule in response to V. cholerae infection when colonized in germfree mice [169].…”