title: Sparfloxacin selects gyrase mutations in first-step Mycoplasma hominis mutants, whereas ofloxacin selects topoisomerase IV mutations.
abstract: The role of mutations in the genes for GyrA and ParC in quinolone resistance in Mycoplasma hominis was studied. Selection with sparfloxacin gave mutations at GyrA83 (Ser-->Leu; Escherichia coli numbering) or GyrA87 (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 ParC80 (Ser-->Ile) or ParC84 (Glu-->Lys), and mutants were four- to eightfold more resistant to ofloxacin but not to sparfloxacin. Selection of second-step mutants from strains with ParC mutations with either quinolone yielded double mutants with additional mutations at GyrA83 (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 showed high levels of resistance to ofloxacin (MICs, 64 to 128 microg/ml) and moderate levels of resistance to sparfloxacin (MICs, 2 to 8 microg/ml). The primary target of ofloxacin in first-step mutants of Mycoplasma hominis was ParC, whereas that for sparfloxacin was GyrA.
authors.affiliation: Department of Pathobiology, University of Washington, Seattle, Washington 98195, USA. kennyg@u.washington.edu
authors.forename: G E
authors.initials: GE
authors.lastname: Kenny
authors.forename: P A
authors.initials: PA
authors.lastname: Young
authors.forename: F D
authors.initials: FD
authors.lastname: Cartwright
authors.forename: K E
authors.initials: KE
authors.lastname: Sjöström
authors.forename: W M
authors.initials: WM
authors.lastname: Huang
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D019535:Mycoplasma hominis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D015242:Ofloxacin / Q000494:pharmacology*; D017354:Point Mutation
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II; C061363:sparfloxacin