title: Two distinct major facilitator superfamily drug efflux pumps mediate chloramphenicol resistance in Streptomyces coelicolor.
abstract: 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-beta-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-beta-naphthylamide has been shown to potentiate drug activity against a gram-positive bacterium.
authors.affiliation: Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Vecchione
authors.forename: Blair
authors.initials: B
authors.lastname: Alexander
authors.forename: Jason K
authors.initials: JK
authors.lastname: Sello
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002702:Chloramphenicol Resistance; D004151:Dipeptides / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D048372:Streptomyces coelicolor / Q000187:drug effects*
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; C474925:phenylalanylarginine-naphthylamide; D012110:Reserpine
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