title: Characterization of cell-to-cell signaling-deficient Pseudomonas aeruginosa strains colonizing intubated patients.
abstract: Cell-to-cell signaling involving N-acyl-homoserine lactone compounds termed autoinducers (AIs) is instrumental to virulence factor production and biofilm development by Pseudomonas aeruginosa. In order to determine the importance of cell-to-cell signaling during the colonization of mechanically ventilated patients, we collected 442 P. aeruginosa pulmonary isolates from 13 patients. Phenotypic characterization showed that 81% of these isolates produced the AI-dependent virulence factors elastase, protease, and rhamnolipids. We identified nine genotypically distinct P. aeruginosa strains. Six of these strains produced AIs [N-butanoyl-homoserine lactone or N-(3-oxo-dodecanoyl)-homoserine lactone] and extracellular virulence factors (elastase, total exoprotease, rhamnolipid, hydrogen cyanide, or pyocyanin) in vitro. Three of the nine strains were defective in the production of both AIs and extracellular virulence factors. Two of these strains had mutational defects in both the lasR and rhlR genes, which encode the N-acyl-homoserine lactone-dependent transcriptional regulators LasR and RhlR, respectively. The third of these AI-deficient strains was only mutated in the lasR gene. Our observations suggest that most, but not all, strains colonizing intubated patients are able to produce virulence factors and that mutations affecting the cell-to-cell signaling circuit are preferentially located in the transcriptional regulator genes.
authors.affiliation: Institut de Microbiologie Fondamentale, Université de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dénervaud
authors.forename: Patrick
authors.initials: P
authors.lastname: TuQuoc
authors.forename: Dominique
authors.initials: D
authors.lastname: Blanc
authors.forename: Sabine
authors.initials: S
authors.lastname: Favre-Bonté
authors.forename: Viji
authors.initials: V
authors.lastname: Krishnapillai
authors.forename: Cornelia
authors.initials: C
authors.lastname: Reimmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Haas
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005838:Genotype; D006801:Humans; D007440:Intubation / Q000009:adverse effects*; D011552:Pseudomonas Infections / Q000097:blood / Q000209:etiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D015183:Restriction Mapping; D015398:Signal Transduction / Q000235:genetics*; D014774:Virulence
chemical_list: D017931:DNA Primers; D004269:DNA, Bacterial