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PLoS One. 2014 Apr 29;9(4):e95936. doi: 10.1371/journal.pone.0095936. eCollection 2014.

A gacS deletion in Pseudomonas aeruginosa cystic fibrosis isolate CHA shapes its virulence.

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INSERM, UMR-S 1036, Biology of Cancer and Infection, Grenoble, France; CNRS, ERL 5261, Bacterial Pathogenesis and Cellular Responses, Grenoble, France; UJF-Grenoble 1, Grenoble, France; CEA, DSV/iRTSV, Grenoble, France.
Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UMR 7255 CNRS - Aix Marseille University, Marseille, France.


Pseudomonas aeruginosa, a human opportunistic pathogen, is capable of provoking acute and chronic infections that are associated with defined sets of virulence factors. During chronic infections, the bacterium accumulates mutations that silence some and activate other genes. Here we show that the cystic fibrosis isolate CHA exhibits a unique virulence phenotype featuring a mucoid morphology, an active Type III Secretion System (T3SS, hallmark of acute infections), and no Type VI Secretion System (H1-T6SS). This virulence profile is due to a 426 bp deletion in the 3' end of the gacS gene encoding an essential regulatory protein. The absence of GacS disturbs the Gac/Rsm pathway leading to depletion of the small regulatory RNAs RsmY/RsmZ and, in consequence, to expression of T3SS, while switching off the expression of H1-T6SS and Pel polysaccharides. The CHA isolate also exhibits full ability to swim and twitch, due to active flagellum and Type IVa pili. Thus, unlike the classical scheme of balance between virulence factors, clinical strains may adapt to a local niche by expressing both alginate exopolysaccharide, a hallmark of membrane stress that protects from antibiotic action, host defences and phagocytosis, and efficient T3S machinery that is considered as an aggressive virulence factor.

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