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 in 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 quinolune structure.