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Antimicrobial Agents and Chemotherapy, March 2005, p. 1067-1075, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.1067-1075.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CmeR Functions as a Transcriptional Repressor for the Multidrug Efflux Pump CmeABC in Campylobacter jejuni

Jun Lin,1,{dagger} Masato Akiba,1,{ddagger} Orhan Sahin,1,§ and Qijing Zhang1*

Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa1

Received 26 April 2004/ Returned for modification 12 July 2004/ Accepted 28 October 2004

CmeABC, a resistance-nodulation-division (RND) type of efflux pump, contributes to Campylobacter resistance to a broad spectrum of antimicrobial agents and is also essential for Campylobacter colonization of the animal intestinal tract by mediation of bile resistance. As one of the main systems for Campylobacter adaptation to different environments, CmeABC is likely subject to control by regulatory elements. We describe the identification of a transcriptional repressor for CmeABC. Insertional mutagenesis of cmeR, an open reading frame immediately upstream of the cmeABC operon, resulted in overexpression of cmeABC, as determined by transcriptional fusion (PcmeABC-lacZ) and immunoblotting with CmeABC-specific antibodies. Overexpression of the efflux pump was correlated with a moderate increase in the level of resistance of the cmeR mutant to several antimicrobials. In vitro, recombinant CmeR bound specifically to the promoter region of cmeABC, precisely, to the inverted repeat sequences in the cmeABC promoter. A single nucleotide deletion between the two half sites of the inverted repeat reduced the level of CmeR binding to the promoter sequence and resulted in overexpression of cmeABC. Together, these findings indicate that cmeR encodes a transcriptional repressor that directly interacts with the cmeABC promoter and modulates the expression of cmeABC. Mutation either in CmeR or in the inverted repeat impedes the repression and leads to enhanced production of the MDR efflux pump.

* Corresponding author. Mailing address: Department of Veterinary Microbiology and Preventive Medicine, 1116 Veterinary Medicine Complex, Iowa State University, Ames, IA 50011. Phone: (515) 294-2038. Fax: (515) 294-8500. E-mail: zhang123{at}iastate.edu.

{dagger} Present address: Department of Animal Science, The University of Tennessee, Knoxville, TN 37996-4574.

{ddagger} Present address: Department of Safety Research, National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan.

§ Present address: Department of Microbiology, Veterinary Faculty, Mustafa Kemal University, Hatay 31034, Turkey.

Antimicrobial Agents and Chemotherapy, March 2005, p. 1067-1075, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.1067-1075.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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