Asymmetric regulation of quorum-sensing receptors drives autoinducer-specific gene expression programs in Vibrio cholerae.

TitleAsymmetric regulation of quorum-sensing receptors drives autoinducer-specific gene expression programs in Vibrio cholerae.
Publication TypeJournal Article
Year of Publication2017
AuthorsHurley, A, Bassler, BL
JournalPLoS Genet
Volume13
Issue5
Paginatione1006826
Date Published2017 May
ISSN1553-7404
KeywordsBacterial Proteins, Feedback, Physiological, Gene Expression Regulation, Bacterial, Homoserine, Ketones, Lactones, Quorum Sensing, Vibrio cholerae
Abstract

Quorum sensing (QS) is a mechanism of chemical communication that bacteria use to monitor cell-population density and coordinate group behaviors. QS relies on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. Vibrio cholerae employs parallel QS circuits that converge into a shared signaling pathway. At high cell density, the CqsS and LuxPQ QS receptors detect the intra-genus and inter-species autoinducers CAI-1 and AI-2, respectively, to repress virulence factor production and biofilm formation. We show that positive feedback, mediated by the QS pathway, increases CqsS but not LuxQ levels during the transition into QS-mode, which amplifies the CAI-1 input into the pathway relative to the AI-2 input. Asymmetric feedback on CqsS enables responses exclusively to the CAI-1 autoinducer. Because CqsS exhibits the dominant QS signaling role in V. cholerae, agonism of CqsS with synthetic compounds could be used to control pathogenicity and host dispersal. We identify nine compounds that share no structural similarity to CAI-1, yet potently agonize CqsS via inhibition of CqsS autokinase activity.

DOI10.1371/journal.pgen.1006826
Alternate JournalPLoS Genet.
PubMed ID28552952
PubMed Central IDPMC5467912