Plasmid-Mediated Quinolone Resistance in Gram-Negative Bacteria
Summary
Plasmid-mediated quinolone resistance (PMQR) has emerged as a critical driver of antimicrobial failure in Gram-negative pathogens. Mobile genetic elements carry a diverse array of resistance determinants, including qnr proteins that protect DNA gyrase and topoisomerase IV, acetyltransferases such as aac(6′)-Ib-cr that modify fluoroquinolones, and efflux pump genes that extrude these drugs from the cell. These plasmids often co-localise with β-lactamase or aminoglycoside-modifying genes, accelerating multidrug resistance. Horizontal transfer of PMQR plasmids among species such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii amplifies their global dissemination. The interplay between PMQR and chromosomal mutations in gyrA or parC further elevates quinolone minimum inhibitory concentrations, undermining treatment of both community-acquired and nosocomial infections. Effective surveillance and novel therapeutic strategies are therefore essential to curb this threat.
Research from Nature Portfolio
Nanoparticle-based delivery of ciprofloxacin and levofloxacin has been shown to overcome both target-site mutations and PMQR in Acinetobacter baumannii clinical isolates, reducing minimum inhibitory concentrations by up to twelvefold and inhibiting biofilm formation more effectively than free drugs. A survey of Pseudomonas aeruginosa isolates from southwest Iran revealed a high prevalence of qnrA, qnrB and qnrS genes on plasmids, with over one third of fluoroquinolone-non-susceptible strains carrying multiple PMQR determinants in combination. In Acinetobacter baumannii from hospital settings, concurrent acquisition of up to five plasmid-associated resistance genes (including qnrS and aac(6′)-Ib-cr) alongside gyrA and parC mutations was documented, highlighting the multifaceted the mechanisms that underpin high-level ciprofloxacin resistance.
Plasmid-Mediated Quinolone Resistance in Gram-Negative Bacteria publication trend
The graph below shows the total number of articles in plasmid-mediated quinolone resistance in gram-negative bacteria across all publications each year (not limited to Nature Index journals).
Technical terms
Plasmid-mediated quinolone resistance (PMQR): Resistance conferred by genes on mobile plasmids that protect target enzymes or modify drugs.
qnr proteins: Pentapeptide repeat proteins that bind to and shield DNA gyrase and topoisomerase IV from quinolones.
aac(6′)-Ib-cr: An acetyltransferase variant that enzymatically inactivates ciprofloxacin and norfloxacin.
Efflux pump: Membrane transporter that expels antibiotics from bacterial cells, lowering intracellular drug concentration.
Target-site mutation: Point alterations in gyrA or parC genes that reduce quinolone binding to DNA gyrase or topoisomerase IV.
References
- Coexistence of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) genes among clinical Pseudomonas aeruginosa isolates in Egypt. BMC Microbiology (2024).
- Ciprofloxacin- and levofloxacin-loaded nanoparticles efficiently suppressed fluoroquinolone resistance and biofilm formation in Acinetobacter baumannii. Scientific Reports (2024).
- Occurrence of plasmid-mediated quinolone resistance genes in Pseudomonas aeruginosa strains isolated from clinical specimens in southwest Iran: a multicentral study. Scientific Reports (2022).
- Impact of target site mutations and plasmid associated resistance genes acquisition on resistance of Acinetobacter baumannii to fluoroquinolones. Scientific Reports (2021).
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation. JAC-Antimicrobial Resistance (2024).
- Phenotypic and genotypic assessment of fluoroquinolones and aminoglycosides resistances in Pseudomonas aeruginosa collected from Minia hospitals, Egypt during COVID-19 pandemic. BMC Infectious Diseases (2024).
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