Topoisomerase mutations associated with in vitro selection of resistance to moxifloxacin in Streptococcus pneumoniae.
We analyzed the frequencies of selection, the order of acquisition, and the mutations selected on moxifloxacin in two wild-type pneumococcal strains, R6 and 5714. The first selection step showed either a single GyrA mutation or no mutation in any of the quinolone resistance-determining regions. Second-step mutants selected had either a second mutation in ParC or in ParE. Moxifloxacin could belong to these fluoroquinolones, which preferentially target GyrA though probably acting equally through both gyrase and topoisomerase IV.
Houssaye
Serge
S
L.R.M.A., INSERM E0004 Université Paris VI, 75270 Paris cedex 06, France.
Gutmann
Laurent
L
Varon
Emmanuelle
E
D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009154:Mutation / Q000235:genetics*; D011804:Quinolines; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D027101:DNA Topoisomerase IV; D004264:DNA Topoisomerases, Type I; D027081:DNA Gyrase; D000077266:Moxifloxacin