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Related Experiment Videos

Fluoroquinolones: structure and target sites.

P G Higgins1, A C Fluit, F J Schmitz

  • 1Institute for Medical Microbiology and Virology, Universitätsklinikum Düsseldorf, Universitätsstrasse 1, Geb. 22.21, 40225 Düsseldorf, Germany. Paul.Higgins@uni-duesseldorf.de

Current Drug Targets
|February 1, 2003
PubMed
Summary
This summary is machine-generated.

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Quinolone antibiotics target bacterial DNA gyrase and topoisomerase IV. Differences in these enzymes between Gram-positive and Gram-negative bacteria explain drug target preference and guide the development of new fluoroquinolones.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Quinolones are crucial antibacterial drugs targeting bacterial DNA gyrase and topoisomerase IV.
  • Target specificity differs between Gram-negative (DNA gyrase) and Gram-positive (topoisomerase IV) bacteria.
  • Resistance mutations occur in conserved regions of these enzymes, with variations between bacterial groups.

Purpose of the Study:

  • To investigate the structural differences in DNA gyrase and topoisomerase IV between Gram-positive and Gram-negative bacteria.
  • To understand the basis of target preference for quinolone antibiotics.
  • To explore how structural modifications in fluoroquinolones affect their target specificity and potency.

Main Methods:

  • Amino acid sequence analysis of DNA gyrase and topoisomerase IV.

Related Experiment Videos

  • In vitro selection of resistance mutations.
  • Comparison of enzyme sensitivity to quinolone drugs.

    • Main Results:

    • Identical resistance mutations occur in conserved enzyme regions, despite sequence differences.
    • Topoisomerase IV shows defined sequence variations between Gram-positive and Gram-negative bacteria.
    • Newer fluoroquinolones can shift the primary target in Gram-positives from topoisomerase IV to DNA gyrase.

    Conclusions:

    • Sequence differences in topoisomerase IV may explain target preference in quinolone antibiotics.
    • Fluoroquinolone modifications can alter antibacterial spectrum and overcome resistance.
    • Understanding enzyme-drug interactions is key for developing next-generation antibiotics.