title: Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa.
abstract: Intrinsic and acquired antibiotic resistance of the nosocomial pathogen Pseudomonas aeruginosa is mediated mainly by the expression of several efflux pumps of broad substrate specificity. Here we report that nfxC type mutants, overexpressing the MexEF-OprN efflux system, produce lower levels of extracellular virulence factors than the susceptible wild type. These include pyocyanin, elastase, and rhamnolipids, three factors controlled by the las and rhl quorum-sensing systems of P. aeruginosa. In agreement with these observations are the decreased transcription of the elastase gene lasB and the rhamnosyltransferase genes rhlAB measured in nfxC type mutants. Expression of the lasR and rhlR regulator genes was not affected in the nfxC type mutant. In contrast, transcription of the C4-homoserine lactone (C4-HSL) autoinducer synthase gene rhlI was reduced by 50% in the nfxC type mutant relative to that in the wild type. This correlates with a similar decrease in C4-HSL levels detected in supernatants of the nfxC type mutant. Transcription of an rhlAB-lacZ fusion could be partially restored by the addition of synthetic C4-HSL and Pseudomonas quinolone signal (PQS). It is proposed that the MexEF-OprN efflux pump affects intracellular PQS levels.
authors.affiliation: Department of Genetics and Microbiology, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland. Thilo.Kohler@medecine.unige.ch
authors.forename: T
authors.initials: T
authors.lastname: Köhler
authors.forename: C
authors.initials: C
authors.lastname: van Delden
authors.forename: L K
authors.initials: LK
authors.lastname: Curty
authors.forename: M M
authors.initials: MM
authors.lastname: Hamzehpour
authors.forename: J C
authors.initials: JC
authors.lastname: Pechere
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D008025:Ligases; D008969:Molecular Sequence Data; D009154:Mutation; D010196:Pancreatic Elastase / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D015363:Quinolones / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C105708:OprN protein, Pseudomonas aeruginosa; D015363:Quinolones; D015534:Trans-Activators; D014157:Transcription Factors; C088386:homoserine lactone; D006602:Hexosyltransferases; C088697:rhamnosyltransferase 1; D010196:Pancreatic Elastase; D008025:Ligases; C096955:RHLI protein, Pseudomonas aeruginosa; D015107:4-Butyrolactone