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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.
AuthorsFabrice V Biot, Eric Valade, Eric Garnotel, Jacqueline Chevalier, Claude Villard, François M Thibault, Dominique R Vidal, Jean-Marie Pagès
JournalPloS one (PLoS One) Vol. 6 Issue 2 Pg. e16892 (Feb 09 2011) ISSN: 1932-6203 [Electronic] United States
PMID21347382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Chloramphenicol
Topics
  • Anti-Bacterial Agents (pharmacology)
  • Burkholderia (cytology, drug effects, genetics, metabolism)
  • Cell Membrane (drug effects, metabolism)
  • Chloramphenicol (pharmacology)
  • Drug Resistance, Multiple (drug effects, genetics)
  • Genes, MDR
  • Mutation
  • Proteomics

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