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J Antimicrob Chemother. 1999 Dec;44(6):735-42.

Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates.

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Microbiology, Department of Clinical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Dr. Pasteur s/n, 35080 Las Palmas, Spain.


Eighteen quinolone-resistant isolates of Escherichia coli were selected by exposing ten clinical isolates to increasing concentrations of norfloxacin and lomefloxacin. The mutant isolates showed a multiple-antibiotic-resistance phenotype. All of them contained single mutations in gyrA consisting of the substitution of Ser-83-->Leu (n = 14), Val (n = 1) or Ala (n = 1) and the substitution of Asp-87-->Asn (n = 2). Only one concomitant mutation in parC (Ser-80-->Arg) was detected. Four parent isolates exhibited a single mutation in gyrA which required < or = 12 mg/L of norfloxacin to be inhibited. Fluoroquinolone resistance, in the 18 quinolone-resistant mutants, was a result of mutations affecting DNA gyrase plus decreased fluoroquinolone uptake. This latter mechanism of resistance was a combined effect of an absence of OmpF and an increase in active efflux in eight isolates, or an increased active efflux alone in the remaining ten selected mutants.

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