title: Development and mechanism of fluoroquinolone resistance in Legionella pneumophila.
abstract: The potential for selection in vitro of Legionella pneumophila mutants resistant to fluoroquinolones was investigated. Six distinct clinical isolates of L. pneumophila were subcultured in subinhibitory concentrations of ciprofloxacin, levofloxacin, clinafloxacin, trovafloxacin and moxifloxacin until MICs increased at least eight-fold. The numbers of serial passages required in microbroth dilution series were determined. The gyrA gene of the six parental strains, and 12 selected mutant strains, was sequenced. The five quinolones differed markedly in their ability to select mutants with decreased susceptibility. The average number of serial passages required was low in the cases of clinafloxacin (n = 10.6), ciprofloxacin and levofloxacin (both n = 13), but notably higher for trovafloxacin (n = 26.6) and moxifloxacin (n = 22.5). Five mutants treated with ciprofloxacin and three treated with moxifloxacin showed Thr83-->Lys or Thr83-->Ile amino acid changes in the gyrA gene. In conclusion, different quinolones lose their antimicrobial effect after a varying number of passages. This study demonstrated, for the first time to our knowledge, that gyrA in L. pneumophila is a possible target of fluoroquinolones.
authors.affiliation: Institute of Environmental Medicine and Hospital of Epidemiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg. djonas@IUK3.UKL.uni-Freiburg.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Jonas
authors.forename: Inge
authors.initials: I
authors.lastname: Engels
authors.forename: Doris
authors.initials: D
authors.lastname: Hartung
authors.forename: Jan
authors.initials: J
authors.lastname: Beyersmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Frank
authors.forename: Franz D
authors.initials: FD
authors.lastname: Daschner
mesh_terms: D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000494:pharmacology*; D003062:Codon / Q000235:genetics; D003470:Culture Media; D027081:DNA Gyrase / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones; D016952:Legionella pneumophila / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000890:Anti-Infective Agents; D003062:Codon; D003470:Culture Media; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D027081:DNA Gyrase