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Antimicrobial Agents and Chemotherapy, January 2000, p. 10-13, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Ineffectiveness of Topoisomerase Mutations in Mediating Clinically Significant Fluoroquinolone Resistance in Escherichia coli in the Absence of the AcrAB Efflux Pump

Margret Oethinger,1,2,3 Winfried V. Kern,4 Angelika S. Jellen-Ritter,4 Laura M. McMurry,1,2 and Stuart B. Levy1,2,5,*

Center for Adaptation Genetics and Drug Resistance1 and the Departments of Molecular Biology and Microbiology2 and of Medicine,5 Tufts University School of Medicine, Boston, Massachusetts 02111, Herz-und Diabeteszentrum NRW, Bad Oeynhausen,3 and Section of Infectious Diseases and Clinical Immunology, University Hospital and Medical Center, Ulm,4 Germany

Received 1 July 1999/Returned for modification 31 August 1999/Accepted 29 September 1999

Fluoroquinolone-resistant mutants, selected from a wild-type Escherichia coli K-12 strain and its Mar mutant by exposure to increasing levels of ofloxacin on solid medium, were analyzed by Northern (RNA) blot analysis, sequencing, and radiolabelled ciprofloxacin accumulation studies. Mutations in the target gene gyrA (DNA gyrase), the regulatory gene marR, and additional, as yet unidentified genes (genes that probably affect efflux mediated by the multidrug efflux pump AcrAB) all contributed to fluoroquinolone resistance. Inactivation of the acrAB locus made all strains, including those with target gene mutations, hypersusceptible to fluoroquinolones and certain other unrelated drugs. These studies indicate that, in the absence of the AcrAB pump, gyrase mutations fail to produce clinically relevant levels of fluoroquinolone resistance.

* Corresponding author. Mailing address: Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-6764. Fax: (617) 636-0458. E-mail: slevy{at}opal.tufts.edu.

Antimicrobial Agents and Chemotherapy, January 2000, p. 10-13, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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