title: Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia.
abstract: OBJECTIVE
  The pathogenesis and the outcome of Pseudomonas aeruginosa ventilator-acquired pneumonia depend on the virulence factors displayed by the bacteria as well as the host response. Thus, quorum sensing, lipopolysaccharide, and type 3 secretion system have each individually been shown to be important virulence systems in laboratory reference strains. However, the relative contribution of these three factors to the in vivo pathogenicity of clinically relevant strains has never been studied. We analyzed the virulence of 56 nonclonal Pseudomonas aeruginosa strains isolated from critically ill patients with ventilator-acquired pneumonia. To avoid the variation of human immune response, we used a murine model of pneumonia. The aim was to determine which virulence factor was the most important.
  
  
  METHODS
  Research laboratory of a university.
  
  
  METHODS
  Male adult BALB/c mice.
  
  
  METHODS
  In vitro, the phenotype of each strain was established as to the expression of quorum sensing-regulated factors (elastase and pyocyanin), type 3 secretion system exotoxin secretion (Exotoxin U, S and/or T, or "nonsecreting"), and lipopolysaccharide O-antigen serotype. Strain pathogenicity was evaluated in vivo in a mouse model of acute pneumonia through lung injury assessment by measuring alveolar-capillary barrier permeability to proteins, lung wet/dry weight ratio, and bacterial dissemination. Associations were then sought between virulence system phenotypes and levels of lung injury.
  
  
  RESULTS
  In univariate analysis, elastase production, O11 serotype, and type 3 secretion system exotoxin secretion were associated with increased lung injury and exotoxin U was linked to an increase risk of bacteremia. In multivariate analysis, we observed that type 3 secretion system exotoxin secretion and to a lesser degree elastase production were associated with increased lung injury.
  
  
  CONCLUSIONS
  In a murine model of pneumonia, our data suggest that type 3 secretion system and elastase are the most important virulence factors in clinically relevant P. aeruginosa strains.
authors.affiliation: Université de Lille II, Faculté de Médecine, U1019, Lille, France. rozenn.leberre@chu-brest.fr
authors.forename: Rozenn
authors.initials: R
authors.lastname: Le Berre
authors.forename: Sophie
authors.initials: S
authors.lastname: Nguyen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nowak
authors.forename: Eric
authors.initials: E
authors.lastname: Kipnis
authors.forename: Maud
authors.initials: M
authors.lastname: Pierre
authors.forename: Lauriane
authors.initials: L
authors.lastname: Quenee
authors.forename: Florence
authors.initials: F
authors.lastname: Ader
authors.forename: Steve
authors.initials: S
authors.lastname: Lancel
authors.forename: René
authors.initials: R
authors.lastname: Courcol
authors.forename: Benoît P
authors.initials: BP
authors.lastname: Guery
authors.forename: Karine
authors.initials: K
authors.lastname: Faure
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000502:physiology; D004195:Disease Models, Animal; D005098:Exotoxins / Q000502:physiology; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D053717:Pneumonia, Ventilator-Associated / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; D037521:Virulence Factors; D008666:Metalloendopeptidases; C043859:pseudolysin, Pseudomonas aeruginosa