title: Involvement of the efflux pumps in chloramphenicol selected strains of Burkholderia thailandensis: proteomic and mechanistic evidence.
abstract: Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections.
authors.affiliation: UMR-MD-1, Facultés de Médecine et de Pharmacie, Université de la Méditerranée, IFR88, Marseille, France.
authors.forename: Fabrice V
authors.initials: FV
authors.lastname: Biot
authors.forename: Eric
authors.initials: E
authors.lastname: Valade
authors.forename: Eric
authors.initials: E
authors.lastname: Garnotel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Claude
authors.initials: C
authors.lastname: Villard
authors.forename: François M
authors.initials: FM
authors.lastname: Thibault
authors.forename: Dominique R
authors.initials: DR
authors.lastname: Vidal
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019117:Burkholderia / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002701:Chloramphenicol / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics*; D019450:Genes, MDR; D009154:Mutation; D040901:Proteomics
chemical_list: D000900:Anti-Bacterial Agents; D002701:Chloramphenicol