Molecular mechanisms of fluoroquinolones resistance in Pseudomonas aeruginosa

Background: Nosocomial infections caused by Pseudomonas aeruginosa are often difficult to treat due to resistance to a wide range of antimicrobial agents. In most countries fluoroquinolones are the only acquirable antibiotics for oral treatment of P. aeruginosa infections. However, P. aeruginosa easily becomes resistant to these antibiotics. The aim of this study was to review the molecular mechanisms of fluoroquinolones resistance in P. aeruginosa. Methods: We’ve searched PubMed, Google scholar, SID and Magiran databases from the year 1985 to 2018 for keywords such as P. aeruginosa, fluoroquinolones resistance, gyrA, par C and efflux pump system among published articles. Results: The results revealed that in P. aeruginosa resistance to fluoroquinolones is mediated primarily through spontaneous mutations in the quinolone resistance- determining regions (QRDR) of the gyrA and parC genes. Other mechanisms include mutations in the regulatory genes of the multidrug efflux pumps systems and innate impermeability of the membrane. A single mutation in the gyrA (Thr-83→ IL) is sufficient for resistance to fluoroquinolones but the accumulation of mutations in the QRDR regions of the gyrA, gyrB, parC, parE and regulatory genes of the multidrug efflux pumps associated with high-level fluoroquinolone resistance. Conclusion: In P. aeruginosa, the main mechanisms of fluoroquinolones resistance are mutations in the gyrA and parC genes, moreover other mechanisms have a complementary role in fluoroquinolones resistance.

Keywords:

P. aeruginosa , fluoroquinolone resistance , gyrA , parC , efflux pump