Mutation in DNA gyrase of norfloxacin-resistant clinical isolates of Neisseria gonorrhoeae.
OBJECTIVE
Recently a rapid decrease in the susceptibility of Neisseria gonorrhoeae isolates to fluoroquinolones has occurred and gonococcal fluoroquinolone resistance is now a significant problem in the treatment of gonorrhoea in Japan. Thus, in order to investigate the quinolone resistance mechanisms in clinical isolates of N gonorrhoeae we studied an alteration in the DNA gyrase subunit A (GyrA) which is well-known as a common mechanism of bacterial quinolone resistance.


METHODS
Four clinical isolates of N gonorrhoeae resistant to norfloxacin and 5 strains susceptible to norfloxacin, including 2 clinical isolates and 3 WHO reference strains, were tested in this study. To identify mutations in the GyrA genes of gonococcal strains, polymerase chain reaction and direct DNA sequencing were performed.


RESULTS
A single base change (serine codon TCC changed to phenylalanine codon TTC), which resulted in an amino acid change in GyrA at position 91, was identified in all 4 norfloxacin-resistant strains for which the MICs of norfloxacin ranged from 1.0 to 8.0 micrograms/ml, while no mutation within GyrA was detected in 5 norfloxacin-susceptible strains for which the MICs of norfloxacin ranged from 0.004 to 0.063 microgram/ml.


CONCLUSIONS
The results from this study suggest that the serine-91 to phenylalanine substitution in GyrA is probably an essential mutation in fluoroquinolone resistance in clinical isolates of N gonorrhoeae.
Tanaka
M
M
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Otsuki
M
M
Nishino
T
T
Kobayashi
I
I
Matsumoto
T
T
Kumazawa
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004352:Drug Resistance, Microbial; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000201:enzymology / Q000235:genetics*; D009643:Norfloxacin / Q000494:pharmacology*; D017354:Point Mutation
D000890:Anti-Infective Agents; D004250:DNA Topoisomerases, Type II; D009643:Norfloxacin