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Antimicrobial Agents and Chemotherapy, April 2004, p. 1128-1135, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1128-1135.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

BpeAB-OprB, a Multidrug Efflux Pump in Burkholderia pseudomallei

Y. Y. Chan, T. M. C. Tan, Y. M. Ong, and K. L. Chua*

Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore

Received 1 July 2003/ Returned for modification 22 September 2003/ Accepted 9 December 2003

Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a wide range of antimicrobial agents, including ß-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.

* Corresponding author: Department of Biochemistry, Faculty of Medicine, National University of Singapore, 8 Medical Dr., Singapore 117597, Singapore. Phone: (65) 68743684. Fax: (65) 67791453. E-mail: bchckl{at}nus.edu.sg.

Antimicrobial Agents and Chemotherapy, April 2004, p. 1128-1135, Vol. 48, No. 4
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.4.1128-1135.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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