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JAC Advance Access published online on January 6, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg054
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Development and mechanism of fluoroquinolone resistance in Legionella pneumophila

Daniel Jonas 1*, Inge Engels 1, Doris Hartung 1, Jan Beyersmann 2, Uwe Frank 1, Franz D. Daschner 1

1 Institute of Environmental Medicine and Hospital of Epidemiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg
2 Freiburg Centre for Data Analysis and Modelling, University of Freiburg and Institute of Medical Biometry and Medical Informatics, University Hospital of Freiburg, Freiburg, Germany

* Corresponding author. E-mail: djonas{at}IUK3.UKL.uni-Freiburg.de.

Received 22 July 2002 ; revised 8 October 2002 ; accepted 22 October 2002

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.

Keywords: fluoroquinolone resistance, gyrA, Legionella pneumophila
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