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Primary targets of fluoroquinolones in Streptococcus pneumoniae

H Fukuda1, K Hiramatsu

  • 1Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan. fvbb0984@mb.infoweb.ne.jp

Antimicrobial Agents and Chemotherapy
|January 30, 1999
PubMed

Insights

Mutations in Streptococcus pneumoniae parC confer resistance to certain fluoroquinolones, indicating topoisomerase IV is their primary target. Conversely, gyrA mutations suggest DNA gyrase is the main target for other fluoroquinolones.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Fluoroquinolones are broad-spectrum antibiotics crucial for treating bacterial infections.
  • Understanding the specific molecular targets of fluoroquinolones in bacteria like Streptococcus pneumoniae is essential for guiding antibiotic development and combating resistance.
  • Streptococcus pneumoniae is a significant human pathogen, and identifying its susceptibility patterns to different antibiotics is clinically relevant.

Purpose of the Study:

  • To elucidate the primary molecular targets of various fluoroquinolones in wild-type Streptococcus pneumoniae.
  • To investigate the mechanisms of fluoroquinolone resistance by analyzing mutations in key bacterial enzymes.

Main Methods:

  • Inducing and isolating fluoroquinolone-resistant mutants of Streptococcus pneumoniae IID553.
  • Utilizing specific fluoroquinolones (trovafloxacin, levofloxacin, norfloxacin, ciprofloxacin, gatifloxacin, sparfloxacin) for selection.
  • Analyzing mutations in the parC and gyrA genes, which encode subunits of topoisomerase IV and DNA gyrase, respectively.
  • Performing cross-resistance assays to determine the spectrum of resistance.

Main Results:

  • Mutants with parC mutations exhibited cross-resistance to trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin, but remained susceptible to gatifloxacin and sparfloxacin.
  • Mutants with gyrA mutations were resistant to gatifloxacin and sparfloxacin, but not to the other tested fluoroquinolones.
  • These findings differentiate the primary targets based on the observed resistance patterns.

Conclusions:

  • In Streptococcus pneumoniae, trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin primarily target topoisomerase IV.
  • Gatifloxacin and sparfloxacin primarily target DNA gyrase in Streptococcus pneumoniae.
  • This differential targeting has implications for understanding and overcoming fluoroquinolone resistance mechanisms.

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