title: Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones.
abstract: gyrA and parC mutations have been identified inn Streptococcus pneumoniae mutants stepwise selected for resistance to sparfloxacin, an antipneumococcal fluoroquinolone. GyrA mutations (at the position equivalent to resistance hot spot Ser-83 in Escherichia coli GyrA) were found in all 17 first-step mutants examined and preceded DNA topoisomerase IV parC mutations (at Ser-79 or Glu-83), which appeared only in second-step mutants. The targeting of gyrase by sparfloxacin in S. pneumoniae but of topoisomerase IV by ciprofloxacin indicates that target preference can be altered by changes in quinolone structure.
authors.affiliation: Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, University of London, United Kingdom.
authors.forename: X S
authors.initials: XS
authors.lastname: Pan
authors.forename: L M
authors.initials: LM
authors.lastname: Fisher
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D027081:DNA Gyrase; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D009154:Mutation; D016133:Polymerase Chain Reaction; D015363:Quinolones / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II; C061363:sparfloxacin