Sparfloxacin selects gyrase mutations in first-step Mycoplasma hominis mutants, whereas ofloxacin selects topoisomerase IV mutations

The role of mutations in the genes for GyrA and ParC in quinolone resistanc e in Mycoplasma hominis was studied. Selection with sparfloxacin gave mutat ions at GyrA83 (Ser-->Leu; Escherichia coli numbering) or GgrA87 (Glu-->Lys ), and mutants had increased levels of resistance to sparfloxacin (8- to 16 -fold) but not to ofloxacin, Selection with ofloxacin gave changes at ParC8 0 (Ser-->Ile) or ParC84 (Glu-->Lys), and mutants were four- to eightfold mo re resistant to ofloxacin but not to sparfloxacin. Selection of second-step mutants from strains with ParC mutations with either quinolone yielded dou ble mutants with additional mutations at GgrA83 (Ser-->Trp or Ser-->Leu) or GyrA87 (Glu-->Lys). Second-step selection of GyrA mutants gave additional mutations at ParC80 (Ser-->Ile) or ParC84 (Glu-->Lys), Two-step mutants sho wed high levels of resistance to ofloxacin MICs, 64 to 128 mu g/ml) and mod erate levels of resistance to sparfloxacin (MICs, 2 to 8 mu g/ml). The prim ary target of ofloxacin in first-step mutants of il Mycoplasma hominis was ParC, whereas that for sparfloxacin was GyrA.