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Antimicrobial Agents and Chemotherapy, July 2005, p. 2807-2815, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2807-2815.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sixteen Homologs of the Mex-Type Multidrug Resistance Efflux Pump in Bacteroides fragilis

Department of Oral Microbiology, Matsumoto Dental University, Shiojiri, Japan,¹ Department of Wadsworth Anaerobe Laboratory, GLAVAHCS, and Department of Medicine, UCLA School of Medicine, Los Angeles, California,² Department of Institute for Oral Science, Matsumoto Dental University, Shiojiri, Japan,³ Department of Microbiology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan⁴

Received 1 September 2004/ Returned for modification 17 October 2004/ Accepted 14 March 2005

Sixteen homologs of multidrug resistance efflux pump operons of the resistance-nodulation-cell division (RND) family were found in the Bacteroides fragilis genome sequence by homology searches. Disruption mutants were made to the mexB homologs of the four genes most similar to Pseudomonas aeruginosa mexB. Reverse transcription-PCR was conducted and indicated that the genes were transcribed in a polycistronic fashion and that the promoter was upstream of bmeA (the mexA homolog). One of these disruption mutants (in bmeB, the mexB homolog) was more susceptible than the parental strain to certain cephems, polypeptide antibiotics, fusidic acid, novobiocin, and puromycin. The gene for this homolog and the adjacent upstream gene, bmeA, were cloned in a hypersensitive Escherichia coli host. The resultant transformants carrying B. fragilis bmeAB were more resistant to certain agents; these agents also had lower MICs for the B. fragilis bmeB disruption mutants than for the parental strain. The putative efflux pump operon is composed of bmeA, bmeB, and bmeC (a putative outer membrane channel protein homologous with OprM). Addition of the efflux pump inhibitors, carbonyl cyanide m-chlorophenylhydrazone (a proton conductor that eliminates the energy source) and Phe-Arg ß-naphthylamide (MC-207,110) (the first specific inhibitor described for RND pumps in P. aeruginosa), resulted in lowered MICs in the parental strain but not in the bmeB disruption mutant, indicating that the bmeB pump is affected by these inhibitors. This is the first description of RND type pumps in the genus Bacteroides.

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