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

J Antimicrob Chemother. 1999 Dec;44(6):735-42. doi: 10.1093/jac/44.6.735.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / chemistry
  • DNA Topoisomerase IV
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • Drug Resistance, Microbial / genetics
  • Drug Resistance, Multiple / genetics
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Infections / microbiology*
  • Fluoroquinolones*
  • Humans
  • Lipopolysaccharides / chemistry
  • Microbial Sensitivity Tests
  • Mutation
  • Norfloxacin / metabolism
  • Norfloxacin / pharmacology*
  • Quinolones / pharmacology*


  • Anti-Infective Agents
  • Bacterial Outer Membrane Proteins
  • Fluoroquinolones
  • Lipopolysaccharides
  • Quinolones
  • DNA Topoisomerase IV
  • DNA Topoisomerases, Type II
  • lomefloxacin
  • Norfloxacin