Interplay between three RND efflux pumps in doxycycline-selected strains of Burkholderia thailandensis.

Autor: Biot FV; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France ; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France., Lopez MM; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France., Poyot T; Pôle de génomique, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France., Neulat-Ripoll F; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France ; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France., Lignon S; FR 3479 Plate-forme de Protéomique, CNRS, Aix-Marseille Université, Marseille, France., Caclard A; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France ; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France., Thibault FM; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France ; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France., Peinnequin A; Pôle de génomique, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France., Pagès JM; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France., Valade E; Unité de Bactériologie/UMR_MD 1, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France ; UMR_MD 1, Aix Marseille Université, IRBA, Facultés de Médecine et de Pharmacie, Marseille, France ; Ecole du Val-de-Grâce, Paris, France.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2013 Dec 27; Vol. 8 (12), pp. e84068. Date of Electronic Publication: 2013 Dec 27 (Print Publication: 2013).
DOI: 10.1371/journal.pone.0084068
Abstrakt: Background: Efflux systems are involved in multidrug resistance in most Gram-negative non-fermentative bacteria. We have chosen Burkholderia thailandensis to dissect the development of multidrug resistance phenotypes under antibiotic pressure.
Methodology/principal Findings: We used doxycycline selection to obtain several resistant B. thailandensis variants. The minimal inhibitory concentrations of a large panel of structurally unrelated antibiotics were determined ± the efflux pump inhibitor phenylalanine-arginine ß-naphthylamide (PAßN). Membrane proteins were identified by proteomic method and the expressions of major efflux pumps in the doxycycline selected variants were compared to those of the parental strains by a quantitative RT-PCR analysis. Doxycycline selected variants showed a multidrug resistance in two major levels corresponding to the overproduction of two efflux pumps depending on its concentration: AmrAB-OprA and BpeEF-OprC. The study of two mutants, each lacking one of these pumps, indicated that a third pump, BpeAB-OprB, could substitute for the defective pump. Surprisingly, we observed antagonistic effects between PAßN and aminoglycosides or some ß-lactams. PAßN induced the overexpression of AmrAB-OprA and BpeAB-OprB pump genes, generating this unexpected effect.
Conclusions/significance: These results may account for the weak activity of PAßN in some Gram-negative species. We clearly demonstrated two antagonistic effects of this molecule on bacterial cells: the blocking of antibiotic efflux and an increase in efflux pump gene expression. Thus, doxycycline is a very efficient RND efflux pump inducer and PAßN may promote the production of some efflux pumps. These results should be taken into account when considering antibiotic treatments and in future studies on efflux pump inhibitors.
Databáze: MEDLINE
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