Covalent inhibition of bacterial quorum sensing

Neri Amara, Roi Mashiach, Dotan Amar, Pnina Krief, Stéphane A.H. Spieser, Matthew J. Bottomley, Amir Aharoni, Michael M. Meijler

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (QS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C12-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence.

Original languageEnglish
Pages (from-to)10610-10619
Number of pages10
JournalJournal of the American Chemical Society
Volume131
Issue number30
DOIs
StatePublished - 5 Aug 2009

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