title: Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system.
abstract: Pseudomonas aeruginosa is an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors. P. aeruginosa infections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoeba Dictyostelium discoideum can be used as a simple model system to analyze the virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum-sensing system were almost as inhibitory as the wild type, while rhl quorum-sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model system, factors controlled by the rhl quorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis of D. discoideum cells. By using this simple model system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa should show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system to assess pathogenicity of P. aeruginosa.
authors: Département de Morphologie, Université de Genève, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland.
authors: Pierre
authors: P
authors: Cosson
authors: Laurence
authors: L
authors: Zulianello
authors: Olivier
authors: O
authors: Join-Lambert
authors: François
authors: F
authors: Faurisson
authors: Leigh
authors: L
authors: Gebbie
authors: Mohammed
authors: M
authors: Benghezal
authors: Christian
authors: C
authors: Van Delden
authors: Lasta Kocjancic
authors: LK
authors: Curty
authors: Thilo
authors: T
authors: Köhler
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001433:Bacteriolysis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004023:Dictyostelium / Q000254:growth & development / Q000382:microbiology*; D004195:Disease Models, Animal; D006017:Glycolipids / Q000494:pharmacology; D006602:Hexosyltransferases / Q000172:deficiency / Q000235:genetics; D008297:Male; D008722:Methods; D009154:Mutation; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D006017:Glycolipids; C081237:LasI protein, Pseudomonas aeruginosa; C080365:LasR protein, Pseudomonas aeruginosa; C086515:RhlR protein, Pseudomonas aeruginosa; D015534:Trans-Activators; C418382:rhamnolipid; D006602:Hexosyltransferases; C088697:rhamnosyltransferase 1