A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes

Meenu Kesarwani, Ronen Hazan, Jianxin He, Yok Ai Que, Yiorgos Apidianakis, Biliana Lesic, Gaoping Xiao, Valérie Dekimpe, Sylvain Milot, Eric Deziel, François Lépine, Laurence G. Rahme

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections.

Original languageAmerican English
Article numbere1002192
JournalPLoS Pathogens
Volume7
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

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