title: A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes.
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.
authors.affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Meenu
authors.initials: M
authors.lastname: Kesarwani
authors.forename: Ronen
authors.initials: R
authors.lastname: Hazan
authors.forename: Jianxin
authors.initials: J
authors.lastname: He
authors.forename: Yok-Ai
authors.initials: YA
authors.lastname: Que
authors.forename: Yokai
authors.initials: Y
authors.lastname: Que
authors.forename: Yiorgos
authors.initials: Y
authors.lastname: Apidianakis
authors.forename: Biliana
authors.initials: B
authors.lastname: Lesic
authors.forename: Gaoping
authors.initials: G
authors.lastname: Xiao
authors.forename: Valérie
authors.initials: V
authors.lastname: Dekimpe
authors.forename: Sylvain
authors.initials: S
authors.lastname: Milot
authors.forename: Eric
authors.initials: E
authors.lastname: Deziel
authors.forename: François
authors.initials: F
authors.lastname: Lépine
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
mesh_terms: D000098:Acetophenones / Q000378:metabolism*; D000208:Acute Disease; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D051379:Mice; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D053038:Quorum Sensing / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators; C055495:2-aminoacetophenone