title: BpeAB-OprB, a multidrug efflux pump in Burkholderia pseudomallei.
abstract: Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a wide range of antimicrobial agents, including beta-lactams, aminoglycosides, macrolides, and polymyxins. An operon, bpeR-bpeA-bpeB-oprB, which encodes a putative repressor, a membrane fusion protein, an inner membrane protein, and an outer membrane protein, respectively, of a multidrug efflux pump of the resistance-nodulation-division family was identified in B. pseudomallei. The divergently transcribed bpeR gene encodes a putative repressor protein of the TetR family which probably regulates the expression of the bpeAB-oprB gene cluster. Comparison of the MICs and minimal bactericidal concentrations of antimicrobials for bpeAB deletion mutant KHW Delta bpeAB and its isogenic wild-type parent, KHW, showed that the B. pseudomallei BpeAB-OprB pump is responsible for the efflux of the aminoglycosides gentamicin and streptomycin, the macrolide erythromycin, and the dye acriflavine. Antibiotic efflux by the BpeAB-OprB pump was dependent on a proton gradient and differs from that by the AmrAB-OprA pump in that it did not efflux the aminoglycoside spectinomycin or the macrolide clarithromycin. The broad-spectrum efflux pump inhibitor MC-207,110 did not potentiate the effectiveness of the antimicrobials erythromycin and streptomycin in B. pseudomallei.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Chan
authors.forename: T M C
authors.initials: TM
authors.lastname: Tan
authors.forename: Y M
authors.initials: YM
authors.lastname: Ong
authors.forename: K L
authors.initials: KL
authors.lastname: Chua
mesh_terms: D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D004151:Dipeptides / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004917:Erythromycin / Q000378:metabolism / Q000494:pharmacology; D017353:Gene Deletion; D015723:Gene Library; D005798:Genes, Bacterial / Q000235:genetics; D005816:Genetic Complementation Test; D018942:Macrolides / Q000378:metabolism / Q000494:pharmacology; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009876:Operon / Q000235:genetics; D033903:Periplasmic Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; C485375:BpeA protein, Burkholderia pseudomallei; C485376:BpeB protein, Burkholderia pseudomallei; D002352:Carrier Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D004151:Dipeptides; D018942:Macrolides; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C485377:OprB protein, Burkholderia pseudomallei; D033903:Periplasmic Proteins; C419365:phenylalanine arginine beta-naphthylamide; D004917:Erythromycin