Development and mechanism of fluoroquinolone resistance in Legionella pneumophila

Daniel Jonas1, Inge Engels, Doris Hartung

  • 1Institute of Environmental Medicine and Hospital of Epidemiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg. djonas@IUK3.UKL.uni-Freiburg.de

Insights

Investigating fluoroquinolone resistance in Legionella pneumophila revealed that different antibiotics vary in their ability to select for resistant mutants. The gyrA gene was identified as a potential target for fluoroquinolone action in this bacterium.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Legionella pneumophila is a significant human pathogen.
  • Fluoroquinolones are critical antibiotics for treating Legionella infections.
  • Understanding resistance mechanisms is crucial for effective treatment.

Purpose of the Study:

  • To investigate the in vitro selection of Legionella pneumophila mutants resistant to various fluoroquinolones.
  • To determine the relative efficiency of different fluoroquinolones in selecting for resistance.
  • To identify potential genetic targets associated with fluoroquinolone resistance.

Main Methods:

  • Subculturing six clinical isolates of L. pneumophila in subinhibitory concentrations of five fluoroquinolones (ciprofloxacin, levofloxacin, clinafloxacin, trovafloxacin, moxifloxacin).
  • Determining minimum inhibitory concentrations (MICs) and the number of serial passages required for resistance development.
  • Sequencing the gyrA gene of parental and mutant strains.

Main Results:

  • Fluoroquinolones exhibited marked differences in their ability to select for resistant L. pneumophila mutants.
  • Fewer passages were required for resistance selection with clinafloxacin, ciprofloxacin, and levofloxacin compared to trovafloxacin and moxifloxacin.
  • Amino acid changes (Thr83 to Lys or Ile) in the gyrA gene were observed in mutants selected by ciprofloxacin and moxifloxacin.

Conclusions:

  • Different fluoroquinolones have varying efficacy in selecting for resistant Legionella pneumophila.
  • The gyrA gene in L. pneumophila is a likely target for fluoroquinolone activity.
  • These findings have implications for antibiotic stewardship and the development of new anti-Legionella therapies.

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