title: Gamma-aminobutyric acid acts as a specific virulence regulator in Pseudomonas aeruginosa.
abstract: Gamma-aminobutyric acid (GABA) is widespread in the environment and can be used by animal and plants as a communication molecule. Pseudomonas species, in particular fluorescent ones, synthesize GABA and express GABA-binding proteins. In this study, we investigated the effects of GABA on the virulence of Pseudomonas aeruginosa. While exposure to GABA (10 µM) did not modify either the growth kinetics or the motility of the bacterium, its cytotoxicity and virulence were strongly increased. The Caenorhabditis elegans 'fast killing test' model revealed that GABA acts essentially through an increase in diffusible toxin(s). GABA also modulates the biofilm formation activity and adhesion properties of PAO1. GABA has no effect on cell surface polarity, biosurfactant secretion or on the lipopolysaccharide structure. The production of several exo-enzymes, pyoverdin and exotoxin A is not modified by GABA but we observed an increase in cyanogenesis which, by itself, could explain the effect of GABA on P. aeruginosa virulence. This mechanism appears to be regulated by quorum sensing. A proteomic analysis revealed that the effect of GABA on cyanogenesis is correlated with a reduction of oxygen accessibility and an over-expression of oxygen-scavenging proteins. GABA also promotes specific changes in the expression of thermostable and unstable elongation factors Tuf/Ts involved in the interaction of the bacterium with the host proteins. Taken together, these results suggest that GABA is a physiological regulator of P. aeruginosa virulence.
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dagorn
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hillion
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Annelise
authors.initials: A
authors.lastname: Chapalain
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesouhaitier
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Duclairoir Poc
authors.affiliation: SIMA, UMR 6014 COBRA, University of Rouen, 27000 Evreux, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vieillard
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: Laboratoire de Biotechnologie et Chimie Marines, Université de Bretagne-Sud B.P. 92116, 56321 Lorient cedex, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Taupin
authors.affiliation: SIMA, UMR 6014 COBRA, University of Rouen, 27000 Evreux, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Le Derf
authors.affiliation: Laboratory of Microbiology Signals and Microenvironment (LMSM) EA 4312, University of Rouen, 27000 Evreux, France.
authors.forename: Marc G J
authors.initials: MGJ
authors.lastname: Feuilloley
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis; D017173:Caenorhabditis elegans / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D020543:Proteome / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D016019:Survival Analysis; D037521:Virulence Factors / Q000096:biosynthesis*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D020543:Proteome; D037521:Virulence Factors; D005680:gamma-Aminobutyric Acid