Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.
Linda Kherroubi1, Joanna Bacon2, Khondaker Miraz Rahman1
1School of Cancer and Pharmaceutical Science, King's College London, London SE1 9NH, UK.
Jac-Antimicrobial Resistance
|August 15, 2024
Summary
Fluoroquinolone antibiotics face increasing bacterial resistance, driven by target enzyme mutations and altered cell membranes. Novel treatments targeting DNA gyrase and topoisomerase IV are crucial to combat resistant Gram-negative pathogens.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The rise of bacterial resistance to quinolone and fluoroquinolone antibiotics since the 1960s poses a significant global health threat.
- The World Health Organization identified critical Gram-negative pathogens like *Klebsiella pneumoniae*, *Acinetobacter baumannii*, *Pseudomonas aeruginosa*, and *Escherichia coli* due to widespread resistance.
Purpose of the Study:
- To review the current understanding of fluoroquinolone resistance mechanisms.
- To highlight the emergence of novel fluoroquinolone-resistant mutants.
- To emphasize the need for developing novel antimicrobial agents and treatments.
Main Methods:
- Literature review of studies investigating fluoroquinolone resistance mechanisms.
- Analysis of genetic mutations in target enzymes (DNA gyrase, topoisomerase IV).
- Examination of the role of porins and efflux pumps in resistance.
Main Results:
- Mutations in DNA gyrase and topoisomerase IV are the primary mechanisms conferring high-level fluoroquinolone resistance.
- Alterations in porins and efflux pumps also contribute significantly to resistance.
- Emergence of novel resistant mutants necessitates the development of new therapeutic strategies.
Conclusions:
- Understanding fluoroquinolone resistance mechanisms is critical for developing effective treatments.
- Novel antimicrobial agents targeting DNA gyrase/topoisomerase IV via alternative pathways are under development.
- Continued research is imperative to combat the growing challenge of antibiotic resistance.
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