Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa

Int J Antimicrob Agents. 2005 Apr;25(4):290-5. doi: 10.1016/j.ijantimicag.2004.11.012.

Abstract

The presence of fluoroquinolone resistance-associated alterations in topoisomerase II and IV were investigated for 103 nfxC-like type Pseudomonas aeruginosa isolates. The most nfxC-like type isolates (98.1%) possessed the substitution of Ile for Thr-83 in GyrA. A single alteration in GyrA (Thr-83-->Ile) was the most frequently detected and the next common alteration was two alterations with Thr-83-->Ile in GyrA and Ser-87-->Leu in ParC. A novel alteration at position Glin-106 of GyrA, which was suggested to be responsible for fluoroquinolone resistance, was identified. Our study revealed that the alterations in GyrB (Glu-468-->Asp) and in ParE (Asp-419-->Asn or Glu-459-->Asp) play a complementary role in the acquisition of resistance to fluoroquinolone. There was a correlation between the ciprofloxacin MIC and the number of resistance-associated alterations in GyrA, GyrB, ParC and ParE of P. aeruginosa isolates.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Ciprofloxacin / pharmacology*
  • DNA Gyrase / genetics*
  • DNA Topoisomerase IV / genetics*
  • Drug Resistance, Bacterial / genetics*
  • Fluoroquinolones / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Mutation*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / genetics

Substances

  • Anti-Infective Agents
  • Fluoroquinolones
  • Ciprofloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase