Mechanism of fluoroquinolone action

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K Drlica1

  • 1Public Health Research Institute 455 First Avenue, New York, NY 10016, USA. drlica@phri.nyu.edu.

Current Opinion in Microbiology
|October 6, 1999
PubMed

Insights

Fluoroquinolones trap bacterial gyrase and topoisomerase IV enzymes with DNA, halting DNA replication and repair. This drug-DNA-enzyme complex formation leads to distinct cellular consequences based on enzyme location.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Fluoroquinolones are a class of antibiotics that target bacterial DNA gyrase and topoisomerase IV.
  • These enzymes are essential for DNA replication, transcription, repair, and recombination.
  • Understanding the precise mechanism of fluoroquinolone action is crucial for developing new antibacterial strategies.

Purpose of the Study:

  • To elucidate the molecular mechanism by which fluoroquinolones interact with bacterial topoisomerases.
  • To investigate the differential physiological consequences of fluoroquinolone-DNA-enzyme complex formation.
  • To understand how enzyme localization affects fluoroquinolone efficacy.

Main Methods:

  • Biochemical assays to study enzyme kinetics and DNA cleavage.
  • Analysis of protein-DNA-drug ternary complex formation.
  • Microbiological studies to assess the impact of fluoroquinolone-induced complexes on bacterial physiology.

Main Results:

  • Fluoroquinolones induce conformational changes in gyrase and topoisomerase IV upon binding to DNA.
  • These antibiotics inhibit DNA religation, leading to enzyme trapping in ternary complexes.
  • Gyrase and topoisomerase IV complexes exhibit distinct physiological effects due to their preferential localization relative to replication forks.

Conclusions:

  • Fluoroquinolone-mediated inhibition of bacterial topoisomerases is a complex process involving enzyme trapping.
  • The spatial arrangement of gyrase and topoisomerase IV influences the cellular outcome of fluoroquinolone treatment.
  • Targeting these enzyme complexes offers a viable strategy for novel antibiotic development.

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