Association of fluoroquinolone resistance with rare quinolone resistance-determining region (QRDR) mutations and protein-quinolone binding affinity (PQBA) in multidrug-resistant Escherichia coli isolated from patients with urinary tract infection
Abstract
BACKGROUND
Urinary tract infections (UTIs) caused by Escherichia coli pose significant public health risks, particularly in developing countries like Bangladesh. This study aimed to elucidate resistance patterns among UTI isolates and comprehensively investigate the mutational spectrum and its impact on drug-microbe interactions.
METHODS
We collected and identified E. coli isolates from hospitalized UTI patients at Dhaka Medical College Hospital and determined their resistance patterns using the disc diffusion method and broth microdilution. Quinolone resistance-determining regions (QRDRs) of the target genes (gyrA, gyrB, parC, and parE) associated with fluoroquinolone resistance were amplified by polymerase chain reaction (PCR) and analyzed through BTSeq™ sequencing for mutations, followed by molecular docking analysis using PyMOL and AutoDock for the protein-quinolone binding affinity (PQBA) study.
RESULTS
All isolates (100 %) displayed multidrug resistance, with chloramphenicol (16 % resistant) and colistin (28 % resistant) demonstrating superior efficacy compared to other antibiotics. The isolates resistant to colistin, as determined by disc diffusion testing, exhibited remarkably high minimum inhibitory concentrations (MICs), with one isolate registering an MIC exceeding 512 µg/mL. Alarming resistance rates were observed for five antibiotic classes, except for polymyxins (28 % resistant) and protein synthesis inhibitors (48 % resistant). Fifty-two percent (52 %) of the…
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