title: MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides.
abstract: Exposure of Pseudomonas aeruginosa to aminoglycosides frequently selects for recalcitrant subpopulations exhibiting an unstable, "adaptive" resistance to these antibiotics. In this study, we investigated the implication in the phenomenon of MexXY-OprM, an active efflux system known to export aminoglycosides in P. aeruginosa. Immunoblotting experiments demonstrated that the transporter MexY, but not the outer membrane pore OprM, was overproduced during the post-drug exposure adaptation period in wild-type strain PAO1. Furthermore, MexY production was dependent upon the degree of bacterial exposure to gentamicin (drug concentration). In contrast to parental strain PAO1, mutants defective in MexXY or in OprM were unable to develop adaptive resistance. Altogether, these results indicate that the resistance process requires the rapid production of MexXY and the interaction of these proteins with the constitutively produced component OprM.
authors.affiliation: Laboratoire de Bactériologie, Hôpital Jean Minjoz, Besançon, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hocquet
authors.forename: Christelle
authors.initials: C
authors.lastname: Vogne
authors.forename: Farid
authors.initials: F
authors.lastname: El Garch
authors.forename: Anne
authors.initials: A
authors.lastname: Vejux
authors.forename: Naomasa
authors.initials: N
authors.lastname: Gotoh
authors.forename: Angela
authors.initials: A
authors.lastname: Lee
authors.forename: Olga
authors.initials: O
authors.lastname: Lomovskaya
authors.forename: Patrick
authors.initials: P
authors.lastname: Plésiat
mesh_terms: D000222:Adaptation, Physiological; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C402791:MexXY protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa