The Association between TLR4 Gene Polymorphism (TLR4-Rs11536889 G/C) and Urinary Tract Infections Caused by Multidrug-Resistant Bacteria among Iraqi Patients

Authors

  • Akram Radhi Al-Rifae General Hospital, Thi-Qar province, Iraq
  • SEÇİL AKILLI ŞİMŞEK‎ College of Science , Çankırı karatekin university‏ ‏‎, Çankırı ,Turkey ‎

DOI:

https://doi.org/10.32792/utq/utjsci/v12i2.1492

Keywords:

Gene polymorphism, Multiple drug resistance, TLR4

Abstract

This current study investigated the association between functional gene polymorphisms Toll-like receptors 4 (TLR4 rs11536889) and susceptibility to multidrug-resistant (MDR) bacterial urinary tract infections (UTIs). A total of 350 urine samples were collected from male and female patients aged 10 to 75 years at Al-Rifae General Hospital in Thi-Qar province, southern Iraq, between July 2022 and January 2023 .All bacterial isolates were identified biochemically and by the VITEK-2 system. All isolates were then confirmed with the 16S rRNA gene and resistance genes were detected using bacterial colonies in a PCR test. Tetra-ARMS-PCR was used to detect TLR4 gene polymorphism (rs11536889). Of these, 150 samples (42.9%) showed positive bacterial growth, while 200 samples (57.1%) were culture-negative. The samples that were positive for bacterial growth were 150 samples, including 30 XDR samples, 20 sensitive to antibiotics, and 100 MDR samples Pathogens isolated from MDR samples included Escherichia coli (44%), Staphylococcus aureus (33%), Klebsiella pneumoniae (10%), and Proteus mirabilis (13%). Genotypic analysis of the TLR4 rs11536889 single nucleotide polymorphism SNP (TLR4  rs11536889) indicated that individuals carrying the homozygous CC and heterozygous GC genotypes exhibited a significantly increased risk of developing MDR UTIs, suggesting a potential role for this SNP (TLR4  rs11536889) in host susceptibility to infection, therefore, this polymorphism may serve as a valuable genetic biomarker for the early diagnosis of UTI susceptibility and could contribute to personalized therapeutic approaches, helping to identify individuals at greater risk for resistant infections and to guide appropriate preventive or treatment strategies.

References

‎[1] ‎ S. Salvatore, E. Cattoni, G. Siesto, M. Serati, P. ‎Sorice, and M. Torella, “Urinary tract infections in ‎women,” Eur. J. Obstet. Gynecol. Reprod. Biol., ‎vol. 156, no. 2, pp. 131–136, 2011.‎

‎[2] ‎ M. Rawal, S. Lamba, N. Agarwal, and A. Kansal, “A ‎prospective microbiological study of urinary tract ‎infection,” IJSR, vol. 7, no. 2, pp. 131–134, 2017.‎

‎[3] ‎ M. E. Terlizzi, G. Gribaudo, and M. E. Maffei, ‎‎“Uropathogenic Escherichia coli infections: ‎virulence factors, bladder responses, antibiotic and ‎non-antibiotic antimicrobial strategies,” Front. ‎Microbiol., vol. 8, pp. 1566–1574, 2017.‎

‎[4] ‎ A. L. Flores-Mireles, J. N. Walker, M. Caparon, and ‎S. J. Hultgren, “Urinary tract infections: ‎epidemiology, mechanisms of infection and ‎treatment options,” Nat. Rev. Microbiol., vol. 13, ‎no. 5, pp. 269–284, 2015.‎

‎[5] ‎ A. P. Magiorakos, A. Srinivasan, R. B. Carey, Y. ‎Carmeli, M. E. Falagas, C. G. Giske, S. Harbarth, J. ‎F. Hindler, G. Kahlmeter, B. Olsson-Liljequist, D. ‎L. Monnet, “Multidrug-resistant, extensively drug-‎resistant and pandrug-resistant bacteria: an ‎international expert proposal for interim standard ‎definitions for acquired resistance,” Clinical ‎Microbiology and Infection, vol. 18, no. 3, pp. ‎‎268–281, 2012.‎‏ ‏T. Hato and P. C. Dagher, “How ‎the innate immune system senses trouble and ‎causes trouble,” Clin. J. Am. Soc. Nephrol., vol. 10, ‎no. 8, p. 1459, 2015.‎

‎[6] ‎ Y. L. Fu and R. E. Harrison, “Microbial phagocytic ‎receptors and their potential involvement in ‎cytokine induction in macrophages,” Front. ‎Immunol., vol. 12, p. 662063, 2021.‎

‎[7] ‎ L. E. Lehmann, S. Hauser, T. Malinka, S. Klaschik, ‎F. Stüber, and M. Book, “Real-time polymerase ‎chain-reaction detection of pathogens is feasible to ‎supplement the diagnostic sequence for urinary ‎tract infections,” BJU International, vol. 106, no. ‎‎1, pp. 114–120, 2010.‎

‎[8] ‎ R. R. Alyethodi, U. Singh, S. Kumar, R. Alex, G. S. ‎Sengar, T. V. Raja, and B. Prakash,

‎“Designing, optimization, and validation of whole ‎blood direct T-ARMS PCR for precise and rapid ‎genotyping of complex vertebral malformation in ‎cattle,” BMC Biotechnology, vol. 21, no. 1, p. 36, ‎‎2021.‎

‎[9] ‎ A. Field, “Discovering Statistics Using SPSS,” 6th ‎ed., SAGE Publications, 2022.‎

‎[10] ‎ Centers for Disease Control and Prevention, ‎Antibiotic Resistance Threats in the United States ‎‎2019. Washington, DC, USA: Department of ‎Health and Human Services, 2019..‎

‎[11] ‎ A. S. H. Sumon, M. R. Al-Mahmood, K. A. ‎Islam, A. E. Karim, P. Aker, A. Ullah, and M. ‎Rashid-Al-Mahmood,“Multidrug resistance ‎urinary tract infection in chronic kidney disease ‎patients: an observational study,” Cureus, vol. 15, ‎no. 5, 2023.‎

‎[12] ‎ Y. Gebretensaie, A. Atnafu, S. Girma, Y. ‎Alemu, and K. Desta,“Prevalence of bacterial ‎urinary tract infection, associated risk factors, and ‎antimicrobial resistance pattern in Addis Ababa, ‎Ethiopia: a cross-sectional study,” Infection and ‎Drug Resistance, pp. 3041–3050, 2023.‎

‎[13] ‎ T. J. Foster, “Antibiotic resistance in ‎Staphylococcus aureus: current status and future ‎prospects,” FEMS Microbiol. Rev., vol. 41, no. 3, ‎pp. 430–449, 2017.‎

‎[14] ‎ J. A. Muqdad, “Molecular study for the ‎isolation and identification of bacteria causing ‎urinary tract infection in pregnant women and the ‎identification of antibiotic resistance genes in ‎southern Iraq,” 2022.‎

‎[15] ‎ R. F. Polse, S. Y. Yousif, and M. S. Assafi, ‎‎“Prevalence and antimicrobial susceptibility ‎patterns of uropathogenic E. coli among people in ‎Zakho, Iraq,” Int. J. Res. Med. Sci., vol. 4, no. 4, pp. ‎‎1219–1223, 2016.‎

‎[16] ‎ I. Simon-Oke, O. Odeyemi, and O. J. Afolabi, ‎‎“Incidence of urinary tract infections and ‎antimicrobial susceptibility pattern among ‎pregnant women in Akure, Nigeria,” Sci. Afr., vol. ‎‎6, p. e00151, 2019.‎

‎[17] ‎ Y. Jin, S. Qiu, N. Shao, and J. Zheng, ‎‎“Association of toll-like receptor gene ‎polymorphisms and its interaction with HPV ‎infection in determining the susceptibility of ‎cervical cancer in Chinese Han population,” ‎Mamm. Genome, vol. 28, pp. 213–219, 2017.‎

‎[18] ‎ W. S. Al-Wazni and B. S. Hadi, “Antivirulence ‎effects of pomegranate peel extracts on most ‎common urinary tract infection pathogens in ‎pregnant women,” J. Contemp. Med. Sci., vol. 1, ‎no. 4, pp. 7–12, 2015.‎

‎[19] ‎ K. Abass, S. K. Adanu, and S. Agyemang, ‎‎“Peri-urbanisation and loss of arable land in ‎Kumasi Metropolis in three decades: evidence ‎from remote sensing image analysis,” Land Use ‎Policy, vol. 72, pp. 470–479, 2018.‎

‎[20] ‎ M. J. Alghizzi, M. Alansari, and A. Shami, ‎‎“The prevalence of Staphylococcus aureus and ‎methicillin-resistant S. aureus in processed food ‎samples in Riyadh, Saudi Arabia,” J. Pure Appl. ‎Microbiol., vol. 15, no. 1, 2021.‎

‎[21] ‎ M. Grazul, E. Balcerczak, and M. Sienkiewicz, ‎‎“Analysis of the presence of the virulence and ‎regulation genes from Staphylococcus aureus in ‎coagulase-negative staphylococci,” Int. J. Environ. ‎Res. Public Health, vol. 20, no. 6, p. 5155, 2023‎‏.‏

‎[22] ‎ T. Zmantar, K. Chaieb, F. Ben Abdallah, A. ‎Ben Kahla-Nakbi, A. Ben Hassen, K. Mahdouani, ‎and A. Bakhrouf,“Multiplex PCR detection of the ‎antibiotic resistance genes in Staphylococcus ‎aureus strains isolated from auricular infections,” ‎Folia Microbiologica, vol. 53, no. 4, pp. 357–362, ‎‎2008.‎

‎[23] ‎ H. Shi,“Epidemiology of CTX-M-type ESBL-‎producing nosocomial Escherichia coli infection in ‎China,” Annals of Clinical Microbiology and ‎Antimicrobials, vol. 14, no. 1, pp. 1–5, 2015.‎

‎[24] ‎ S. A. Al-Sheboul, G. S. Al-Madi, B. Brown, and ‎W. A. Hayajneh, “Prevalence of extended-‎spectrum β-lactamases in multidrug-resistant ‎Klebsiella pneumoniae isolates in Jordanian ‎hospitals,” J. Epidemiol. Glob. Health, pp. 1–11, ‎‎2023.‎

‎[25] ‎ A. A. Mwakyoma,“Allele distribution and ‎phenotypic resistance to ciprofloxacin and ‎gentamicin among ESBL-producing Escherichia ‎coli isolated from urine, stool, animals, and ‎environments in Tanzania,” Frontiers in ‎Antibiotics, vol. 2, p. 1164016, 2023.‎

‎[26] ‎ M. Shaaban, S. L. Elshaer, and O. A. Abd El-‎Rahman, “Prevalence of ESBLs, AmpC, and ‎carbapenemases in Proteus mirabilis clinical ‎isolates,” BMC Microbiol., vol. 22, no. 1, p. 247, ‎‎2022.‎

‎[27] ‎ F. O. Enogiomwan and I. N. Ibeh, “Forward and ‎reverse characterization of the CTX-M genes ‎associated with multidrug resistant Escherichia ‎coli in pregnant mothers,” Acta Sci. Microbiol., ‎vol. 1, no. 1, pp. 21–24, 2018.‎

‎[28] ‎ N. S. Lhwak and Y. A. Abbas, “Detection of ‎ESBL gene CTX-M-1 in E. coli and Klebsiella ‎pneumoniae isolated from UTI in pregnant women ‎in Al-Nassyriah City,” Univ. Thi-Qar J. Sci., vol. 2, ‎no. 4, pp. 92–96, 2018.‎

‎[29] ‎ N. Castano-Rodriguez,“Genetic ‎polymorphisms in the Toll-like receptor signalling ‎pathway in Helicobacter pylori infection and ‎related gastric cancer,” Human Immunology, vol. ‎‎75, no. 8, pp. 808–815, 2014.‎

‎[30] ‎ H. J. Kim, J. S. Bae, I. H. Chang, K. D. Kim, J. ‎Lee, H. D. Shin, … & S. C. Myung, “Sequence ‎variants of toll-like receptor 4 (TLR4) and the risk ‎of prostate cancer in Korean men,” World J. Urol., ‎vol. 30, no. 2, pp. 225–232, 2012.‎

‎[31] ‎ K. G. E. Miedema,“Association of ‎polymorphisms in the TLR4 gene with the risk of ‎developing neutropenia in children with ‎leukemia,” Leukemia, vol. 25, no. 6, pp. 995–1000, ‎‎2011.V. Ballén, V. Cepas, C. Ratia, Y. Gabasa, and ‎S. M. Soto, “Clinical Escherichia coli: from ‎biofilm formation to new antibiofilm strategies,” ‎Microorganisms, vol. 10, no. 6, p. 1103, 2022.‎

Downloads

Published

2025-12-28

Issue

Section

Articles

Categories

How to Cite

Radhi, A., & SEÇİL AKILLI ŞİMŞEK‎. (2025). The Association between TLR4 Gene Polymorphism (TLR4-Rs11536889 G/C) and Urinary Tract Infections Caused by Multidrug-Resistant Bacteria among Iraqi Patients. University of Thi-Qar Journal of Science, 12(2), 123-130. https://doi.org/10.32792/utq/utjsci/v12i2.1492