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Antimicrobial Agents and Chemotherapy, November 2009, p. 4673-4677, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00853-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Two Distinct Major Facilitator Superfamily Drug Efflux Pumps Mediate Chloramphenicol Resistance in Streptomyces coelicolor{triangledown}

James J. Vecchione,1 Blair Alexander Jr.,2 and Jason K. Sello1*

Department of Chemistry, Brown University, 324 Brook Street, Providence, Rhode Island 02912,1 Department of Biology, Morehouse College, 830 Westview Drive, S.W., Atlanta, Georgia 303142

Received 24 June 2009/ Returned for modification 27 July 2009/ Accepted 5 August 2009

Chloramphenicol, florfenicol, and thiamphenicol are used as antibacterial drugs in clinical and veterinary medicine. Two efflux pumps of the major facilitator superfamily encoded by the cmlR1 and cmlR2 genes mediate resistance to these antibiotics in Streptomyces coelicolor, a close relative of Mycobacterium tuberculosis. The transcription of both genes was observed by reverse transcription-PCR. Disruption of cmlR1 decreased the chloramphenicol MIC 1.6-fold, while disruption of cmlR2 lowered the MIC 16-fold. The chloramphenicol MIC of wild-type S. coelicolor decreased fourfold and eightfold in the presence of reserpine and Phe-Arg-β-naphthylamide, respectively. These compounds are known to potentiate the activity of some antibacterial drugs via efflux pump inhibition. While reserpine is known to potentiate drug activity against gram-positive bacteria, this is the first time that Phe-Arg-β-naphthylamide has been shown to potentiate drug activity against a gram-positive bacterium.

* Corresponding author. Mailing address: Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912. Phone: (401) 863-1194. Fax: (401) 863-9046. E-mail: Jason_Sello{at}Brown.edu

{triangledown} Published ahead of print on 17 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4673-4677, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00853-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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