The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran

Abstract

The aim of this study was to examine mutations in the quinolone-resistance-determining region (QRDR) of gyrA and parC genes in Pseudomonas aeruginosa isolates. A total of 100 clinical P. aeruginosa isolates were collected from different university-affiliated hospitals in Tabriz, Iran. Minimum inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were evaluated by agar dilution assay. DNA sequences of the QRDR of gyrA and parC were determined by the dideoxy chain termination method. Of the total 100 isolates, 64 were resistant to ciprofloxacin. No amino acid alterations were detected in gyrA or parC genes of the ciprofloxacin susceptible or ciprofloxacin intermediate isolates. Thr-83 → Ile substitution in gyrA was found in all 64 ciprofloxacin resistant isolates. Forty-four (68.75%) of them had additional substitution in parC. A correlation was found between the number of the amino acid alterations in the QRDR of gyrA and parC and the level of ciprofloxacin and levofloxacin resistance of the P. aeruginosa isolates. Ala-88 → Pro alteration in parC was generally found in high level ciprofloxacin resistant isolates, which were suggested to be responsible for fluoroquinolone resistance. These findings showed that in P. aeruginosa, gyrA was the primary target for fluoroquinolone and additional mutation in parC led to highly resistant isolates.

Changes in Outer Membrane Proteins of Benzalkonium Chloride Adapted Pseudomonas Aeruginosa and Mutations in GyrA and ParC Genes

“…The results of mutations detected in GyrA and ParC genes are consistent with previous reports on clinical isolates of P. aeruginosa adapted to BC [28][29][30][31] .…”

“…So Thr-83 -> Ile was shown to be the chief mechanism of fluoroquinolones resistance. This observation confirmed that the DNA gyrase was the primary target for fluoroquinolone resistance in the clinical isolates of P. aeruginosa [30] .…”

Double-Serine Fluoroquinolone Resistance Mutations Advance Major International Clones and Lineages of Various Multi-Drug Resistant Bacteria

“…In addition, authors observed that the fitness cost was influenced by the genotype of the type III secretion system harbored by the isolates (Agnello et al, 2016 ). Moreover, the dominance of the gyrA Thr83Ile alteration often associated with the parC Ser87Leu change in fluoroquinolone resistant strains of P. aeruginosa (Higgins et al, 2003 ; Lee et al, 2005 ; Agnello and Wong-Beringer, 2012 ; Yang et al, 2015 ; Araujo et al, 2016 ; Nouri et al, 2016 ) argues strongly for the salient role of the double-threonine/serine mutations in selecting groups of bacteria with favorable fitness also in this species.…”

Characterization of Klebsiella pneumoniae associated with cattle infections in southwest China using multi-locus sequence typing (MLST), antibiotic resistance and virulence-associated gene profile analysis

“…The ciprofloxacin is widely used in the treatment of K. pneumoniae infections in recent years, and the increasing resistance to fluoroquinolones among K. pneumoniae has also been reported 5, 6. Fluoroquinolones act by inhibiting the action of target enzymes, DNA gyrase and topoisomerase IV, with both enzymes playing a principal role in DNA replication 7 . Some researchers think that alterations in the quinoloneresistance-determining region (QRDR) within DNA gyrase ( gyrA and gyrB ) and topoisomerase IV ( parC and parE ) are the major mechanisms one for fluoroquinolone resistance in K. pneumoniae 6 …”