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
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 impa...
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Elsevier
2025-06-01
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| Series: | Journal of Infection and Public Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1876034125001157 |
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| author | Md Rasel Khan Manik Israt Dilruba Mishu Zimam Mahmud Muntaha Noor Muskan Sharmin Zaman Emon |
| author_facet | Md Rasel Khan Manik Israt Dilruba Mishu Zimam Mahmud Muntaha Noor Muskan Sharmin Zaman Emon |
| author_sort | Md Rasel Khan Manik |
| collection | DOAJ |
| description | 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 isolates exhibited resistance to all five tested quinolones. Sequence analysis revealed a novel L88Q mutation in ParC, affecting PQBA and binding conformation. Additionally, three ParC mutations (S80I, E84V, and E84G) and two ParE mutations (S458A and I529L) were identified, which had not been previously reported in Bangladesh. Among these, S80I appeared in all isolates. Double-mutations (S83L+D87N) in GyrA, L88Q and S80I in ParC, and I529L in ParE were identified as key drivers of fluoroquinolone resistance. Conclusion: Our findings underscore the accumulation of significant mutations within QRDRs of UTI isolates, potentially compromising fluoroquinolone efficacy. The emergence of these novel mutations warrants further investigation to impede their dissemination and combat quinolone resistance. |
| format | Article |
| id | doaj-art-478e93d6aa2142d1af43fa70f42dbb31 |
| institution | DOAJ |
| issn | 1876-0341 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Journal of Infection and Public Health |
| spelling | doaj-art-478e93d6aa2142d1af43fa70f42dbb312025-08-20T02:48:22ZengElsevierJournal of Infection and Public Health1876-03412025-06-0118610276610.1016/j.jiph.2025.102766Association 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 infectionMd Rasel Khan Manik0Israt Dilruba Mishu1Zimam Mahmud2Muntaha Noor Muskan3Sharmin Zaman Emon4Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, BangladeshDepartment of Microbiology, University of Dhaka, Dhaka 1000, Bangladesh; Corresponding authors.Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh; Corresponding authors.Department of Microbiology, University of Dhaka, Dhaka 1000, BangladeshCentre for Advanced Research in Sciences, University of Dhaka, Dhaka 1000, BangladeshBackground: 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 isolates exhibited resistance to all five tested quinolones. Sequence analysis revealed a novel L88Q mutation in ParC, affecting PQBA and binding conformation. Additionally, three ParC mutations (S80I, E84V, and E84G) and two ParE mutations (S458A and I529L) were identified, which had not been previously reported in Bangladesh. Among these, S80I appeared in all isolates. Double-mutations (S83L+D87N) in GyrA, L88Q and S80I in ParC, and I529L in ParE were identified as key drivers of fluoroquinolone resistance. Conclusion: Our findings underscore the accumulation of significant mutations within QRDRs of UTI isolates, potentially compromising fluoroquinolone efficacy. The emergence of these novel mutations warrants further investigation to impede their dissemination and combat quinolone resistance.http://www.sciencedirect.com/science/article/pii/S1876034125001157Urinary tract infectionsAntimicrobial resistanceFluoroquinolonesQRDR mutationsPQBA |
| spellingShingle | Md Rasel Khan Manik Israt Dilruba Mishu Zimam Mahmud Muntaha Noor Muskan Sharmin Zaman Emon 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 Journal of Infection and Public Health Urinary tract infections Antimicrobial resistance Fluoroquinolones QRDR mutations PQBA |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Urinary tract infections Antimicrobial resistance Fluoroquinolones QRDR mutations PQBA |
| url | http://www.sciencedirect.com/science/article/pii/S1876034125001157 |
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