Roles of gyrA mutations in resistance of clinical isolates and in vitro mutants of Bacteroides fragilis to the new fluoroquinolone trovafloxacin.
We determined whether gyrA mutations were present in fluoroquinolone-resistant laboratory mutants derived from the Bacteroides fragilis reference strain ATCC 25285 and in clinical isolates of B. fragilis. The two first-step mutants selected on ciprofloxacin (CIP) were devoid of gyrA mutations, whereas two of the three CIP-selected second-step mutants studied presented the same gyrA mutation leading to a Ser82Phe change. Unusual GyrA alterations, Asp81Asn or Ala118Val, were detected in two of the three first-step mutants selected on trovafloxacin (TRO), Mt3 and Mt1, respectively. The Ala118Val change had no effect on the susceptibility of Mt1 to CIP. No second-step mutant could be obtained with TRO as a selector. For the 12 clinical isolates studied, a Ser82Phe change in GyrA was found only in the 3 strains which showed the highest levels of TRO resistance (MIC, 4 microgram/ml). Thus, the resistance phenotypes and genotypes observed in fluoroquinolone-resistant clinical isolates of B. fragilis were similar to those found in CIP-selected laboratory mutants, whereas peculiar mutational events could be selected in vitro with TRO.
Bachoual
R
R
Service de Bactériologie-Virologie-Hygiène, Hôpital Henri Mondor, Créteil, France.
Dubreuil
L
L
Soussy
C J
CJ
Tankovic
J
J
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001441:Bacteroides fragilis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000502:physiology; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology; D024841:Fluoroquinolones; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009287:Naphthyridines / Q000494:pharmacology*; D009643:Norfloxacin / Q000494:pharmacology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; C080163:trovafloxacin; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II; D009643:Norfloxacin