Non-gyrA-mediated ciprofloxacin resistance in laboratory mutants of Streptococcus pneumoniae

J Antimicrob Chemother. 1997 May;39(5):609-15. doi: 10.1093/jac/39.5.609.

Abstract

Two strains of Streptococcus pneumoniae, M4 (NCTC 7465, type strain) and M5 (clinical isolate), and their respective ciprofloxacin-resistant mutants, M4/C1, M5/C1 and M5/C3, were evaluated. All mutants were stable after one year's storage and all grew more slowly in Brain Heart Infusion broth than the parent. The MICs of ciprofloxacin, sparfloxacin and tosufloxacin were increased for the mutants of M4, whereas the mutants of M5 were less susceptible to ciprofloxacin only. The optimal bactericidal concentration (OBC) of each quinolone for all the strains was approximately ten-fold greater than the MIC. The OBCs for the mutants were increased for ciprofloxacin, but not for the other two quinolones. The DNA synthesis IC50 values of all quinolones correlated well with the MIC of each drug. All quinolones accumulated rapidly within all five strains; 10 mM magnesium chloride decreased the concentration of quinolone accumulated, but carbonyl cyanide m-chlorophenyl hydrazone had no effect. Mutant strains M4/C1, M5/C1 and M5/C3 accumulated less quinolone than their respective parent strains. DNA sequencing of those regions of gyrA and gyrB corresponding to the quinolone resistance-determining region in other bacteria did not reveal any differences between the parent and mutant strains.

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / pharmacology*
  • Base Sequence
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / pharmacology*
  • DNA Gyrase
  • DNA Topoisomerases, Type II / physiology*
  • Drug Resistance, Microbial
  • Molecular Sequence Data
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / growth & development

Substances

  • Anti-Infective Agents
  • Ciprofloxacin
  • DNA Gyrase
  • DNA Topoisomerases, Type II

Associated data

  • GENBANK/U37560