Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates.
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.
Tavío
M M
MM
Microbiology, Department of Clinical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Dr. Pasteur s/n, 35080 Las Palmas, Spain. mtavio@infovia.ulpgc.es
Vila
J
J
Ruiz
J
J
Ruiz
J
J
Martín-Sánchez
A M
AM
Jiménez de Anta
M T
MT
D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology*; D024841:Fluoroquinolones; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009643:Norfloxacin / Q000378:metabolism / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D024841:Fluoroquinolones; D008070:Lipopolysaccharides; D015363:Quinolones; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II; C053091:lomefloxacin; D009643:Norfloxacin