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Antimicrobial Agents and Chemotherapy, February 2003, p. 665-669, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.665-669.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

AcrAB Multidrug Efflux Pump Is Associated with Reduced Levels of Susceptibility to Tigecycline (GAR-936) in Proteus mirabilis

Melissa A. Visalli,* Ellen Murphy, Steven J. Projan, and Patricia A. Bradford

Wyeth Research, Pearl River, New York

Received 28 June 2002/ Returned for modification 7 October 2002/ Accepted 10 November 2002

Tigecycline has good broad-spectrum activity against many gram-positive and gram-negative pathogens with the notable exception of the Proteeae. A study was performed to identify the mechanism responsible for the reduced susceptibility to tigecycline in Proteus mirabilis. Two independent transposon insertion mutants of P. mirabilis that had 16-fold-increased susceptibility to tigecycline were mapped to the acrB gene homolog of the Escherichia coli AcrRAB efflux system. Wild-type levels of decreased susceptibility to tigecycline were restored to the insertion mutants by complementation with a clone containing a PCR-derived fragment from the parental wild-type acrRAB efflux gene cluster. The AcrAB transport system appears to be associated with the intrinsic reduced susceptibility to tigecycline in P. mirabilis.

* Corresponding author. Mailing address: Department of Infectious Disease, Wyeth Research, Room 3218, Bldg. 200, 401 North Middletown Rd., Pearl River, NY 10965. Phone: (845) 602-5203. Fax: (845) 602-5671. E-mail: visallm{at}wyeth.com.

Antimicrobial Agents and Chemotherapy, February 2003, p. 665-669, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.665-669.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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