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Antimicrobial Agents and Chemotherapy, January 2000, p. 10-13, Vol. 44, No. 1
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.
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
*
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.
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