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Antimicrobial Agents and Chemotherapy, March 1999, p. 465-470, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Efflux-Mediated Aminoglycoside and Macrolide Resistance in Burkholderia pseudomallei

Richard A. Moore, David DeShazer, Shauna Reckseidler, Ania Weissman, and Donald E. Woods*

Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1

Received 25 June 1998/Returned for modification 1 September 1998/Accepted 14 December 1998

Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a wide range of antimicrobial agents including beta -lactams, aminoglycosides, macrolides, and polymyxins. We used Tn5-OT182 to mutagenize B. pseudomallei to identify the genes involved in aminoglycoside resistance. We report here on the identification of AmrAB-OprA, a multidrug efflux system in B. pseudomallei which is specific for both aminoglycoside and macrolide antibiotics. We isolated two transposon mutants, RM101 and RM102, which had 8- to 128-fold increases in their susceptibilities to the aminoglycosides streptomycin, gentamicin, neomycin, tobramycin, kanamycin, and spectinomycin. In addition, both mutants, in contrast to the parent, were susceptible to the macrolides erythromycin and clarithromycin but not to the lincosamide clindamycin. Sequencing of the DNA flanking the transposon insertions revealed a putative operon consisting of a resistance, nodulation, division-type transporter, a membrane fusion protein, an outer membrane protein, and a divergently transcribed regulator protein. Consistent with the presence of an efflux system, both mutants accumulated [3H]dihydrostreptomycin, whereas the parent strain did not. We constructed an amr deletion strain, B. pseudomallei DD503, which was hypersusceptible to aminoglycosides and macrolides and which was used successfully in allelic exchange experiments. These results suggest that an efflux system is a major contributor to the inherent high-level aminoglycoside and macrolide resistance found in B. pseudomallei.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1. Phone: (403) 220-2564. Fax: (403) 283-5241. E-mail: woods{at}acs.ucalgary.ca.

Antimicrobial Agents and Chemotherapy, March 1999, p. 465-470, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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