title: High occurrence of simultaneous mutations in target enzymes and MtrRCDE efflux system in quinolone-resistant Neisseria gonorrhoeae.
abstract: BACKGROUND
  Emergence of multidrug-resistant Neisseria gonorrhoeae resulting from new genetic mutations is a serious threat to controlling gonorrhea.
  
  
  OBJECTIVE
  To determine 1) antimicrobial susceptibilities and the corresponding genetic mutations and 2) the role of MtrRCDE efflux system in gonococcal resistance to fluoroquinolones.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This study reports simultaneous mutations in fluoroquinolone target enzymes and the MtrRCDE efflux system as a fluoroquinolone-resistant mechanism in N. gonorrhoeae.
authors.affiliation: Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Beti Ernawati
authors.initials: BE
authors.lastname: Dewi
authors.forename: Sasaki
authors.initials: S
authors.lastname: Akira
authors.forename: Hideo
authors.initials: H
authors.lastname: Hayashi
authors.forename: William
authors.initials: W
authors.lastname: Ba-Thein
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005287:Ferredoxin-NADP Reductase; D024841:Fluoroquinolones / Q000494:pharmacology*; D006069:Gonorrhea / Q000382:microbiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D015242:Ofloxacin / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics*; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D010406:Penicillins; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D002939:Ciprofloxacin; D015242:Ofloxacin; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D013752:Tetracycline