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Prevalence of the fluoroquinolone resistance genes in the Escherichia coli sequence type 131 clone isolated from hospitalized patients with urinary tract infection
Mehdi Bozorgi Mazandarani1 , Mohammad Kargar2 , Farshid Kafilzadeh1
1- Department of Microbiology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
2- Department of Microbiology, Zand Institute of Higher Education, Shiraz, Iran , microkargar@gmail.com
Abstract:   (1093 Views)
Background: The emergence of fluoroquinolones (FQ) resistance in the Escherichia coli (E. coli) sequence type 131 (ST131) has become a major challenge in the management of urinary tract infections (UTI). Chromosomal mutations and plasmid-mediated quinolone resistance (PMQR) determinants play an important role in the FQ resistance.
Methods: This cross-sectional study was conducted in 2020 on 300 urine samples. aimed to investigate the prevalence of the chromosomal mutations, the PMQR genes including qnr, aac (6′)-Ib-cr, and efflux pumps among the FQ-resistant ST131 and non-ST131 E. coli causing UTI.  Initially, the ST131 clone was detected using allele-specific PCR and confirmed by multilocus sequence typing.
Results:  Among 95 FQ-resistant E. coli isolates, 30%  (n=29/95) as belonging to the ST131 clone. The most frequently detected PMQR genes in FQ-resistant isolates were aac(6)’-lb-cr and qnrS. However, statistical analysis revealed a stronger association between aac(6ʹ)-Ib-cr and the ST131 clone (62%; p<0.03). The oqxA gene was the most prevalent efflux pump gene observed in both ST131 (n=11; 38%) and non-ST131 (n=16; 24%) isolates. Analysis of the gyrA and parC genes revealed significantly higher in ST131 compared to non-ST131. Double mutations, S80I+E84V, were significantly more prevalent in both gyrA (76% ST131 vs. 43% non-ST131; p=0.004) and parC (55% ST131 vs. 26% non-ST131; p=0.002). High-level resistance (MIC ≥32 μg/mL) observed in 96.6% (n=28/29) of ST131 isolates compared to 65% (n=43/66) of non-ST131 isolates.
Conclusion: The double mutations confer high level resistance to FQs in ST131 clone. These findings on resistance mechanisms can guide infection control strategies.
Keywords: mutation, plasmid, drug resistance, quinolones, fluoroquinolones
Full-Text [PDF 415 kb]   (308 Downloads)    
Research Article: Original Paper | Subject: bacteriology
Received: 2024/11/1 | Accepted: 2025/03/15
References
1. Kim Y, Kim B, Wie SH, Kim J, Ki M, Cho YK, et al. Fluoroquinolone can be an effective treatment option for acute pyelonephritis when the minimum inhibitory concentration of levofloxacin for the causative Escherichia coli is ≤ 16 mg/L. Antibiotics. 2021;10(1):37. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. Wagenlehner FM, Wagenlehner C, Redman R, Weidner W, Naber KG. Urinary bactericidal activity of doripenem versus that of levofloxacin in patients with complicated urinary tract infections or pyelonephritis. Antimicrob Agents Chemother. 2009;53(4):1567-73. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Nicolas-Chanoine M-H, Blanco J, Leflon-Guibout V, Demarty R, Alonso MP, Caniça MM, et al. Intercontinental emergence of Escherichia coli clone O25: H4-ST131 producing CTX-M-15. J Antimicrob Chemother. 2008;61(2):273-81. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Clermont O, Dhanji H, Upton M, Gibreel T, Fox A, Boyd D, et al. Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains. J Antimicrob Chemother. 2009;64(2):274-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Ismail MD, Ali I, Hatt S, Salzman EA, Cronenwett AW, Marrs CF, et al. Association of Escherichia coli ST131 lineage with risk of urinary tract infection recurrence among young women. J Glob Antimicrob Resist. 2018;13:81-4. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Minarini LA, Darini ALC. Mutations in the quinolone resistance-determining regions of gyrA and parC in Enterobacteriaceae isolates from Brazil. Braz J Microbiol. 2012;43:1309-14. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Ruiz J. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother. 2003;51(5):1109-17. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Hooper DC, Jacoby GA. Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci. 2015;1354(1):12-31. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Azargun R, Gholizadeh P, Sadeghi V, Hosainzadegan H, Tarhriz V, Memar MY, et al. Molecular mechanisms associated with quinolone resistance in Enterobacteriaceae: review and update. Trans R Soc Trop Med Hyg. 2020;114(10):770-81. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Yamane K, Wachino J-i, Suzuki S, Arakawa Y. Plasmid-mediated qepA gene among Escherichia coli clinical isolates from Japan. Antimicrob Agents Chemother. 2008;52(4):1564-6. [View at Publisher] [DOI] [PMID] [Google Scholar]
11. Zhou J, Zhou J, Chen M, Lü P, Jiang C. Prevalence of β-lactam antibiotic resistance of Escherichia coli isolated from a neonatal intensive care unit. BMC Pediatr. 2025;25(1):95. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Wayne P. Clinical and Laboratory Standards Institute: Annapolis Junction. MD, USA. 2025.
13. Hammond DS, Schooneveldt JM, Nimmo GR, Huygens F, Giffard PM. bla SHV genes in Klebsiella pneumoniae: different allele distributions are associated with different promoters within individual isolates. Antimicrob Agents Chemother. 2005;49(1):256-63. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Johnson JR, Clermont O, Johnston B, Clabots C, Tchesnokova V, Sokurenko E, et al. Rapid and specific detection, molecular epidemiology, and experimental virulence of the O16 subgroup within Escherichia coli sequence type 131. J Clin Microbiol. 2014;52(5):1358-65. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Clermont O, Lavollay M, Vimont S, Deschamps C, Forestier C, Branger C, et al. The CTX-M-15-producing Escherichia coli diffusing clone belongs to a highly virulent B2 phylogenetic subgroup.J Antimicrob Chemother. 2008;61(5):1024-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
16. Zhao L, Zhang J, Zheng B, Wei Z, Shen P, Li S, et al. Molecular epidemiology and genetic diversity of fluoroquinolone-resistant Escherichia coli isolates from patients with community-onset infections in 30 Chinese county hospitals. J Clin Microbiol. 2015;53(3):766-70. [View at Publisher] [DOI] [PMID] [Google Scholar]
17. Cattoir V, Poirel L, Rotimi V, Soussy C-J, Nordmann P. Multiplex PCR for detection of plasmid-mediated quinolone resistance qnr genes in ESBL-producing enterobacterial isolates. J Antimicrob Chemother. 2007;60(2):394-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
18. Cavaco LM, Hasman H, Xia S, Aarestrup FM. qnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovar Kentucky and Bovismorbificans strains of human origin. Antimicrob Agents Chemother. 2009;53(2):603-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
19. Platell JL, Cobbold RN, Johnson JR, Heisig A, Heisig P, Clabots C, et al. Commonality among fluoroquinolone-resistant sequence type ST131 extraintestinal Escherichia coli isolates from humans and companion animals in Australia. Antimicrob Agents Chemother. 2011;55(8):3782-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
20. Wang M, Guo Q, Xu X, Wang X, Ye X, Wu S, et al. New plasmid-mediated quinolone resistance gene, qnrC, found in a clinical isolate of Proteus mirabilis. Antimicrob Agents Chemother. 2009;53(5):1892-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
21. Chen X, Zhang W, Pan W, Yin J, Pan Z, Gao S, et al. Prevalence of qnr, aac (6′)-Ib-cr, qepA, and oqxAB in Escherichia coli isolates from humans, animals, and the environment. Antimicrob Agents Chemother. 2012;56(6):3423-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
22. Dalhoff A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdiscip Perspect Infect Dis. 2012:2012:976273. [View at Publisher] [DOI] [PMID] [Google Scholar]
23. Nicolas-Chanoine M-H, Bertrand X, Madec J-Y. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev. 2014;27(3):543-74. [View at Publisher] [DOI] [PMID] [Google Scholar]
24. Damavandi M-S, Gholipour A, Pour ML. Prevalence of class D carbapenemases among extended-spectrum β-lactamases producing Escherichia coli isolates from educational hospitals in Shahrekord. J Clin Diagn Res. 2016;10(5):DC01-5. [View at Publisher] [DOI] [PMID] [Google Scholar]
25. Afsharikhah S, Ghanbarpour R, Mohseni P, Adib N, Bagheri M, Jajarmi M. High prevalence of β-lactam and fluoroquinolone resistance in various phylotypes of Escherichia coli isolates from urinary tract infections in Jiroft city, Iran. BMC Microbiol. 2023;23(1):114. [View at Publisher] [DOI] [PMID] [Google Scholar]
26. Akgoz M, Akman I, Ates AB, Celik C, Keskin B, Ozmen Capin BB, et al. Plasmidic fluoroquinolone resistance genes in fluoroquinolone-resistant and/or extended spectrum Beta-Lactamase-Producing Escherichia coli Strains Isolated from Pediatric and adult patients diagnosed with urinary tract infection. Microb Drug Resist. 2020;26(11):1334-41. [View at Publisher] [DOI] [PMID] [Google Scholar]
27. Bullens M, de Cerqueira Melo A, Raziq S, Lee J, Khalid G, Khan S, et al. Antibiotic resistance in patients with urinary tract infections in Pakistan. Public Health Action. 2022;12(1):48-52. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Zeng Q, Xiao S, Gu F, He W, Xie Q, Yu F, et al. Antimicrobial resistance and molecular epidemiology of uropathogenic Escherichia coli isolated from female patients in Shanghai, China. Frontiers in cellular and infection microbiology. 2021;11:653983. [DOI] [PMID]
29. McDermott E. The threat of antibiotic resistance on global health. 2019.
30. Rasoulinasab M, Shahcheraghi F, Feizabadi MM, Nikmanesh B, Hajihasani A, Aslani MM. Distribution of ciprofloxacin-resistance genes among ST131 and non-ST131 clones of Escherichia coli isolates with ESBL phenotypes isolated from women with urinary tract infection. Iranian Journal of Microbiology. 2021;13(3):294. [DOI:10.18502/ijm.v13i3.6389] [PMID] []
31. Hiasa H. DNA topoisomerases as targets for antibacterial agents. DNA topoisomerases: Methods and protocols. 2018:47-62. [DOI:10.1007/978-1-4939-7459-7_3] [PMID]
32. Spencer AC, Panda SS. DNA Gyrase as a Target for Quinolones. Biomedicines. 2023;11(2):371. [DOI:10.3390/biomedicines11020371] [PMID] []
33. Heisig P. Genetic evidence for a role of parC mutations in development of high-level fluoroquinolone resistance in Escherichia coli. Antimicrobial agents and chemotherapy. 1996;40(4):879-85. [DOI:10.1128/AAC.40.4.879] [PMID] []
34. Hajihasani A, Ebrahimi-Rad M, Rasoulinasab M, Aslani MM, Shahcheraghi F. The Molecular Characterization and Risk Factors of ST131 and Non-ST131 Escherichia coli in Healthy Fecal Carriers in Tehran, Iran. Jundishapur Journal of Microbiology. 2022;15(5). [DOI:10.5812/jjm-122468]
35. Reyna-Flores F, Barrios H, Garza-Ramos U, Sánchez-Pérez A, Rojas-Moreno T, Uribe-Salas FJ, et al. Molecular epidemiology of Escherichia coli O25b-ST131 isolates causing community-acquired UTIs in Mexico. Diagnostic Microbiology and Infectious Disease. 2013;76(3):396-8. [DOI:10.1016/j.diagmicrobio.2013.03.026] [PMID]
36. Bush NG, Diez-Santos I, Sankara Krishna P, Clavijo B, Maxwell A. Insights into antibiotic resistance promoted by quinolone exposure. Antimicrobial Agents and Chemotherapy. 2025;69(1):e00997-24. [DOI:10.1128/aac.00997-24] [PMID] []
37. Serwacki P, Hareza D, Gajda M, Świątek-Kwapniewska W, Adamowska M, Serwacka K, et al. Fluoroquinolone consumption and resistance after an Antibiotic Stewardship Team intervention-an interventional study in a single hospital in southern Poland from 2018-2023. American Journal of Infection Control. 2025. [DOI:10.1016/j.ajic.2025.01.017] [PMID]
38. Nikaido H, Pagès J-M. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS microbiology reviews. 2012;36(2):340-63. [DOI:10.1111/j.1574-6976.2011.00290.x] [PMID] []
39. Li J, Zhang H, Ning J, Sajid A, Cheng G, Yuan Z, et al. The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrobial Resistance & Infection Control. 2019;8:1-13. [DOI:10.1186/s13756-019-0489-3] [PMID] []
40. Ghotaslou R, Baghbani S, Ghotaslou P, Mirmahdavi S, Leylabadlo HE. Molecular epidemiology of antibiotic-resistant Escherichia coli among clinical samples isolated in Azerbaijan, Iran. Iranian Journal of Microbiology. 2023;15(3):383. [DOI:10.18502/ijm.v15i3.12898] [PMID] []
41. Johnson JR, Menard M, Johnston B, Kuskowski MA, Nichol K, Zhanel GG. Epidemic clonal groups of Escherichia coli as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to 2004. Antimicrobial agents and chemotherapy. 2009;53(7):2733-9. [DOI:10.1128/AAC.00297-09] [PMID] []
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