Investigating the Relationship Between Mutations in gyrA and parC Genes and Resistance to Fluoroquinolones in Uropathogenic Escherichia coli Isolates

Introduction: Fluoroquinolone resistance in Escherichia coli , particularly uropathogenic E. coli (UPEC), is a growing concern worldwide. This study investigates the association between mutations in the gyrA and parC genes and fluoroquinolone resistance in UPEC isolates from Urine samples in Iran. Materials and Methods: In total, 150 UPEC isolates were collected, and then, 12 ciprofloxacin-resistant isolates were selected for molecular analysis. Antimicrobial susceptibility testing was performed using the disk diffusion method, and minimum inhibitory concentrations (MICs) of ciprofloxacin were determined by microbroth dilution. Polymerase chain reaction and sequencing were used to detect mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC . Results: All isolates had MIC >4 and were resistant to all four fluoroquinolones and quinolones tested, including ciprofloxacin, norfloxacin, ofloxacin, and nalidixic acid. All isolates harbored mutations in both genes. The most frequent mutations in gyrA were Ser-83→Leu and Asp-87→Asn, found in 100% of isolates. Similarly, mutations in parC , including Ser-80→Ile (83.3%) and Glu-84→Val (58.3%), were prevalent. Additional nucleotide substitutions in both genes were observed. These mutations likely contribute to the high-level fluoroquinolone resistance observed in the isolates. Conclusions: The results of this study confirm that mutations in the gyrA and parC genes primarily drive fluoroquinolone resistance in UPEC isolates. The presence of specific alterations within the QRDRs significantly reduces bacterial susceptibility to fluoroquinolones, contributing to the persistence and spread of resistant strains. Identifying these mutations provides critical insights into resistance mechanisms, which can aid in developing more effective antimicrobial therapy strategies.