Related Experiment Videos
[Mechanisms of bacterial resistance to quinolones]
R Taléns-Visconti1, T M Garrigues, E Cantón
1Unidad de Bacteriología Experimental, Centro de Investigación, Hospital Universitario La Fe, Valencia, España.
Abstract:
In order to produce their cytotoxic effect, quinolones must enter the cell through the bacterial membrane to reach their target, DNA-gyrase or topoisomerase IV, and induce cell death. The mechanisms of resistance to fluoroquinolones include: those mediated by gene mutations codifying for DNA gyrase and topoisomerase IV and leading to QRDR; those characterized by changes in the permeability of the outer membrane which decrease intracellular penetration of the drug; and those caused by active endogenous carriers responsible for drug efflux. These resistance mechanisms can occur alone or in combination; in fact, it is believed that high resistance levels to quinolones in vivo are associated with simultaneous mechanisms. This article reviews such resistance mechanisms and establishes, when possible, their relation to the structure of quinolones.
Insights
Fluoroquinolones kill bacteria by targeting DNA gyrase and topoisomerase IV. Resistance arises from mutations, reduced drug entry, or efflux pumps, often acting together.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Context:
- Quinolones are critical antibiotics targeting bacterial DNA replication.
- Bacterial resistance necessitates understanding drug-target interactions and cellular transport.
- Fluoroquinolone resistance impacts treatment efficacy.
Purpose:
- To review quinolone resistance mechanisms.
- To correlate resistance with quinolone structure.
- To understand how bacteria evade fluoroquinolone antibiotics.
Summary:
- Quinolones require cell entry to inhibit DNA gyrase/topoisomerase IV.
- Resistance involves target mutations (QRDR), altered membrane permeability, and active drug efflux.
- Combined mechanisms often lead to high-level in vivo resistance.
Impact:
- Informs development of new antibiotics.
- Guides strategies to overcome fluoroquinolone resistance.
- Enhances understanding of bacterial survival mechanisms.