High occurrence of simultaneous mutations in target enzymes and MtrRCDE efflux system in quinolone-resistant Neisseria gonorrhoeae

Sex Transm Dis. 2004 Jun;31(6):353-9. doi: 10.1097/00007435-200406000-00007.

Abstract

Background: Emergence of multidrug-resistant Neisseria gonorrhoeae resulting from new genetic mutations is a serious threat to controlling gonorrhea.

Goal: To determine 1) antimicrobial susceptibilities and the corresponding genetic mutations and 2) the role of MtrRCDE efflux system in gonococcal resistance to fluoroquinolones.

Study design: Antimicrobial susceptibility testing and sequence analysis of gyrA, parC, and mtrR loci of 131 N. gonorrhoeae isolates from Japan.

Results: The proportion of N. gonorrhoeae strains resistant and intermediate-resistant to antimicrobials was 25.2% and 48.9% for ciprofloxacin, 25.2% and 30.5% for ofloxacin, 12.2% and 53.4% for penicillin; and 17.6% and 51.1% for tetracycline, respectively. Strains were categorized into 22 mutation profiles, with GyrA-S91F/ParC-D86N/MtrR-G45D being the most predominant profile. The frequency of mutation in gyrA, parC, mtrR, and the mtrR promoter was 71%, 47.3%, 77.1%, and 23.7%, respectively. Seventy-one percent of strains carried mutations in both gyrA and mtrR.

Conclusion: This study reports simultaneous mutations in fluoroquinolone target enzymes and the MtrRCDE efflux system as a fluoroquinolone-resistant mechanism in N. gonorrhoeae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Bacterial Proteins*
  • Ciprofloxacin / pharmacology
  • DNA Gyrase / genetics
  • DNA Topoisomerase IV / genetics
  • Drug Resistance, Bacterial / genetics*
  • Ferredoxin-NADP Reductase*
  • Fluoroquinolones / pharmacology*
  • Gonorrhea / microbiology*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Mutation
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / enzymology*
  • Neisseria gonorrhoeae / genetics
  • Ofloxacin / pharmacology
  • Penicillins / pharmacology
  • Repressor Proteins / genetics*
  • Tetracycline / pharmacology

Substances

  • Anti-Infective Agents
  • Bacterial Proteins
  • Fluoroquinolones
  • Penicillins
  • Repressor Proteins
  • mtrR protein, Neisseria gonorrhoeae
  • Ciprofloxacin
  • Ofloxacin
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • DNA Topoisomerase IV
  • DNA Gyrase
  • Tetracycline