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Updated: Jan 31, 2026
08:58
Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
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Fluoroquinolones: action and resistance.
1Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA. drlica@phri.org
Current Topics in Medicinal Chemistry
|February 7, 2003
Summary
Fluoroquinolones inhibit bacterial growth by trapping DNA gyrase and topoisomerase IV. Understanding the mutant prevention concentration (MPC) is crucial for limiting fluoroquinolone resistance in pathogens.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Fluoroquinolones are antibiotics that target bacterial DNA gyrase and topoisomerase IV.
- These enzymes are essential for DNA replication, transcription, and repair.
- Bacterial resistance to fluoroquinolones is a growing public health concern.
Purpose of the Study:
- To elucidate the mechanism of fluoroquinolone action and resistance.
- To define the mutant prevention concentration (MPC) for fluoroquinolones.
- To identify strategies for minimizing the development of fluoroquinolone resistance.
Main Methods:
- Studies with resistant bacterial mutants.
- Analysis of fluoroquinolone-protein-DNA interactions.
- Pharmacokinetic and pharmacodynamic modeling.
Main Results:
- Fluoroquinolones form ternary complexes with DNA gyrase/topoisomerase IV, inhibiting DNA replication and transcription.
- Resistance mechanisms include altered drug permeability, efflux pumps, protective proteins, and target mutations.
- A mutant prevention concentration (MPC) threshold can be defined to restrict resistance development.
- Suboptimal dosing and cross-resistance erode fluoroquinolone efficacy.
Conclusions:
- Optimizing fluoroquinolone regimens, including combination therapy with pharmacokinetic overlap, can minimize resistance.
- Understanding MPC is vital for selecting effective fluoroquinolones and preventing resistance.
- Continued research into fluoroquinolone-DNA gyrase interactions is needed to combat resistance.
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