Skip to content
2000
image of Investigating Molecular Biomarkers in E. coli-Induced Urinary Tract Infections: Insights into the Long Non-Coding RNAs Contribution to Antimicrobial Resistance

Abstract

Introduction

Urinary Tract Infections (UTIs) caused by are a major concern due to rising antimicrobial resistance. Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation, but their involvement in UTIs and their implication in antimicrobial resistance mechanisms are not well understood. This study investigates the association between specific long non-coding RNAs, immune response, and antibiotic resistance in patients with infections caused by .

Methods

Quantification of specific lncRNAs (NEAT1-1, NEAT1-2, MIR3142HG, AK170409, and IL7AS) was performed using quantitative PCR. Inflammatory markers IL-1β, IRF3, and NF-κB were measured in UTI patients using ELISA kits to assess their biological response. The minimum inhibitory concentration of eleven antibiotics was determined by testing all 25 urine samples and categorized as sensitive, intermediate, or resistant.

Results

NEAT1-1, NEAT1-2, MIR3142HG, and AK170409 were significantly upregulated ( < 0.05). Inflammatory markers were significantly elevated in all samples: IL-1β at 72.36±13.8pg/mL, IRF3 at 79.36±15.01pg/mL, and NF-κB at 4.43±0.82pg/mL

( < 0.0001). NEAT1-2 and AK170409 expression correlated with distinct antibiotic response patterns ( < 0.05). Differences in biological and hematological data were observed among UTI patients with varying topographic expressions of specific long non-coding RNAs (lncRNAs).

discussions

Specific lncRNAs may be involved in modulating immune responses and influencing antibiotic susceptibility in UTIs. Their expression patterns reflect both the severity of infection and resistance profiles, suggesting a functional role in the development of antimicrobial resistance.

Conclusion

LncRNAs are potential biomarkers for UTIs caused by E. coli. Future studies should focus on elucidating their role in the development of antibiotic resistance and exploring their patentable applications in biotechnology.

Loading

Article metrics loading...

/content/journals/biot/10.2174/0118722083388214250924193840
2025-10-06
2025-11-06
Loading full text...

Full text loading...

References

  1. Prasada S. Bhat A. Bhat S. Shenoy Mulki S. Tulasidas S. Changing antibiotic susceptibility pattern in uropathogenic Escherichia coli over a period of 5 years in a tertiary care center. Infect. Drug Resist. 2019 12 1439 1443 10.2147/IDR.S201849 31239723
    [Google Scholar]
  2. He Y. Zhao J. Wang L. Epidemiological trends and predictions of urinary tract infections in the global burden of disease study 2021. Sci. Rep. 2025 15 1 4702 10.1038/s41598‑025‑89240‑5 39922870
    [Google Scholar]
  3. Yang X. Chen H. Zheng Y. Qu S. Wang H. Yi F. Disease burden and long-term trends of urinary tract infections: A worldwide report. Front. Public Health 2022 10 888205 10.3389/fpubh.2022.888205 35968451
    [Google Scholar]
  4. Assouma F.F. Sina H. Adjobimey T. Susceptibility and virulence of Enterobacteriaceae isolated from urinary tract infections in Benin. Microorganisms 2023 11 1 213 10.3390/microorganisms11010213 36677505
    [Google Scholar]
  5. Medina M. Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther. Adv. Urol. 2019 11 1756287219832172 10.1177/1756287219832172 31105774
    [Google Scholar]
  6. Czajkowski K. Broś-Konopielko M. Teliga-Czajkowska J. Urinary tract infection in women. Przegl. Menopauz. 2021 20 1 40 47 10.5114/pm.2021.105382 33935619
    [Google Scholar]
  7. Zagaglia C. Ammendolia M.G. Maurizi L. Nicoletti M. Longhi C. Urinary tract infections caused by uropathogenic Escherichia coli strains—new strategies for an old pathogen. Microorganisms 2022 10 7 1425 10.3390/microorganisms10071425 35889146
    [Google Scholar]
  8. Whelan S. Lucey B. Finn K. Uropathogenic Escherichia coli (UPEC)-associated urinary tract infections: The molecular basis for challenges to effective treatment. Microorganisms 2023 11 9 2169 10.3390/microorganisms11092169 37764013
    [Google Scholar]
  9. Mahshouri P. Alikhani M.Y. Momtaz H.E. Doosti-Irani A. Shokoohizadeh L. Analysis of phylogroups, biofilm formation, virulence factors, antibiotic resistance and molecular typing of uropathogenic Escherichia coli strains isolated from patients with recurrent and non-recurrent urinary tract infections. BMC Infect. Dis. 2025 25 1 267 10.1186/s12879‑025‑10635‑w 39994590
    [Google Scholar]
  10. Turcu F.L. Vacaroiu I.A. Balcangiu-Stroescu A.E. Recurrent urinary tract infections in female patients—A clinical review. J Mind Med Sci 2025 12 1 5 10.3390/jmms12010005
    [Google Scholar]
  11. Jensen M.L.V. Siersma V. Sّes LM, Nicolaisdottir D, Bjerrum L, Holzknecht BJ. Prior antibiotic use increases risk of urinary tract infections caused by resistant Escherichia coli among elderly in primary care: A case-control study. Antibiotics 2022 11 10 1382 10.3390/antibiotics11101382 36290040
    [Google Scholar]
  12. Ku J.H. Bruxvoort K.J. Salas S.B. Multidrug resistance of Escherichia coli from outpatient uncomplicated urinary tract infections in a large United States integrated healthcare organization. Open Forum Infect. Dis. 2023 10 7 ofad287 10.1093/ofid/ofad287 37426945
    [Google Scholar]
  13. Klein R.D. Hultgren S.J. Urinary tract infections: Microbial pathogenesis, host–pathogen interactions and new treatment strategies. Nat. Rev. Microbiol. 2020 18 4 211 226 10.1038/s41579‑020‑0324‑0 32071440
    [Google Scholar]
  14. Walker M.M. Roberts J.A. Rogers B.A. Harris P.N.A. Sime F.B. Current and emerging treatment options for multidrug resistant Escherichia coli urosepsis: A review. Antibiotics 2022 11 12 1821 10.3390/antibiotics11121821 36551478
    [Google Scholar]
  15. Russell S.K. Harrison J.K. Olson B.S. Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome. Nat. Microbiol. 2023 8 5 875 888 10.1038/s41564‑023‑01346‑6 37037942
    [Google Scholar]
  16. Hou Y. Lv Z. Hu Q. Zhu A. Niu H. The immune mechanisms of the urinary tract against infections. Front. Cell. Infect. Microbiol. 2025 15 1540149 10.3389/fcimb.2025.1540149 40308964
    [Google Scholar]
  17. Uszczynska-Ratajczak B. Lagarde J. Frankish A. Guigَ R, Johnson R. Towards a complete map of the human long non-coding RNA transcriptome. Nat. Rev. Genet. 2018 19 9 535 548 10.1038/s41576‑018‑0017‑y 29795125
    [Google Scholar]
  18. Mattick J.S. Amaral P.P. Carninci P. Long non-coding RNAs: Definitions, functions, challenges and recommendations. Nat. Rev. Mol. Cell Biol. 2023 24 6 430 447 10.1038/s41580‑022‑00566‑8 36596869
    [Google Scholar]
  19. Wu H. Yang L. Chen L.L. The diversity of long noncoding RNAs and their generation. Trends Genet. 2017 33 8 540 552 10.1016/j.tig.2017.05.004 28629949
    [Google Scholar]
  20. Heydarnezhad Asl M. Pasban Khelejani F. Bahojb Mahdavi S.Z. Emrahi L. Jebelli A. Mokhtarzadeh A. The various regulatory functions of long noncoding RNAs in apoptosis, cell cycle, and cellular senescence. J. Cell. Biochem. 2022 123 6 995 1024 10.1002/jcb.30221 35106829
    [Google Scholar]
  21. Shin J.J. Park J. Shin H.S. Arab I. Suk K. Lee W.H. Roles of lncRNAs in NF-κB-mediated macrophage inflammation and their implications in the pathogenesis of human diseases. Int. J. Mol. Sci. 2024 25 5 2670 10.3390/ijms25052670 38473915
    [Google Scholar]
  22. Zhang Y. Liu H. Niu M. Roles of long noncoding RNAs in human inflammatory diseases. Cell Death Discov. 2024 10 1 235 10.1038/s41420‑024‑02002‑6 38750059
    [Google Scholar]
  23. Arunima A. van Schaik E.J. Samuel J.E. The emerging roles of long non-coding RNA in host immune response and intracellular bacterial infections. Front. Cell. Infect. Microbiol. 2023 13 1160198 10.3389/fcimb.2023.1160198 37153158
    [Google Scholar]
  24. Shi L. Han X. Liu F. Review on long non-coding RNAs as biomarkers and potentially therapeutic targets for bacterial infections. Curr. Issues Mol. Biol. 2024 46 7 7558 7576 10.3390/cimb46070449 39057090
    [Google Scholar]
  25. Cheng Y. Liang Y. Tan X. Liu L. Host long noncoding RNAs in bacterial infections. Front. Immunol. 2024 15 1419782 10.3389/fimmu.2024.1419782 39295861
    [Google Scholar]
  26. Ginn L. La Montagna M. Wu Q. Shi L. Diverse roles of long non‐coding RNAs in viral diseases. Rev. Med. Virol. 2021 31 4 e2198 10.1002/rmv.2198
    [Google Scholar]
  27. Li Z. Gao J. Xiang X. Deng J. Gao D. Sheng X. Viral long non-coding RNA regulates virus life-cycle and pathogenicity. Mol. Biol. Rep. 2022 49 7 6693 6700 10.1007/s11033‑022‑07268‑6 35301646
    [Google Scholar]
  28. Barry G. Briggs J.A. Hwang D.W. The long non-coding RNA NEAT1 is responsive to neuronal activity and is associated with hyperexcitability states. Sci. Rep. 2017 7 1 40127 10.1038/srep40127 28054653
    [Google Scholar]
  29. Hadjicharalambous M.R. Roux B.T. Feghali-Bostwick C.A. Murray L.A. Clarke D.L. Lindsay M.A. Long non-coding RNAs are central regulators of the IL-1β-induced inflammatory response in normal and idiopathic pulmonary lung fibroblasts. Front. Immunol. 2018 9 2906 10.3389/fimmu.2018.02906 30619270
    [Google Scholar]
  30. Covarrubias S. Robinson E.K. Shapleigh B. CRISPR/Cas-based screening of long non-coding RNAs (lncRNAs) in macrophages with an NF-κB reporter. J. Biol. Chem. 2017 292 51 20911 20920 10.1074/jbc.M117.799155 29051223
    [Google Scholar]
  31. Zhou L. Xing C. Zhou D. Yang R. Cai M. Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p. Open Med. 2020 15 1 986 996 10.1515/med‑2020‑0219 33344773
    [Google Scholar]
  32. Rahman M.M. Hossain M.M.K. Rubaya R. Association of antibiotic resistance traits in uropathogenic Escherichia coli (UPEC) isolates. Can. J. Infect. Dis. Med. Microbiol. 2022 2022 1 9 10.1155/2022/4251486 35340918
    [Google Scholar]
  33. ضztürk R, Murt A. Epidemiology of urological infections: A global burden. World J. Urol. 2020 38 11 2669 2679 10.1007/s00345‑019‑03071‑4 31925549
    [Google Scholar]
  34. Bernaitis L. Priya B. Ezhilarasu A. Shenoy R.P. Isolation and molecular characterization of multi-drug resistant uropathogenic Escherichia coli from urine samples: Insights into urinary tract infection management. Microbe 2024 5 100185 10.1016/j.microb.2024.100185
    [Google Scholar]
  35. Huang L. Huang C. Yan Y. Sun L. Li H. Urinary tract infection etiological profiles and antibiotic resistance patterns varied among different age categories: A retrospective study from a tertiary general hospital during a 12-year period. Front. Microbiol. 2022 12 813145 10.3389/fmicb.2021.813145 35154037
    [Google Scholar]
  36. Fathy F.E. Abdel Salam S.A. Ahmed Y.M. Antimicrobial profile of pathogens causing community acquired urinary tract infection in Ain Shams University hospitals. Egypt. J. Med. Microbiol. 2023 32 2 17 24
    [Google Scholar]
  37. Silva A. Costa E. Freitas A. Almeida A. Revisiting the frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections. Antibiotics 2022 11 6 768 10.3390/antibiotics11060768 35740174
    [Google Scholar]
  38. Xie Z. Jian J. Chen L. Analysis of antimicrobial susceptibility in bacterial pathogens associated with urinary tract infections from Beijing Teaching Hospital in China, 2009–2017. Can. J. Infect. Dis. Med. Microbiol. 2023 2023 1 8 10.1155/2023/4360342 37529141
    [Google Scholar]
  39. Cheng B. Zaman M. Cox W. Correlation of pyuria and bacteriuria in acute care. Am. J. Med. 2022 135 9 e353 e358 10.1016/j.amjmed.2022.04.022 35580716
    [Google Scholar]
  40. Lacerda Mariano L. Ingersoll M.A. The immune response to infection in the bladder. Nat. Rev. Urol. 2020 17 8 439 458 10.1038/s41585‑020‑0350‑8 32661333
    [Google Scholar]
  41. Cornelis G. Souquere S. Vernochet C. Heidmann T. Pierron G. Functional conservation of the lncRNA NEAT1 in the ancestrally diverged marsupial lineage: Evidence for NEAT1 expression and associated paraspeckle assembly during late gestation in the opossum Monodelphis domestica. RNA Biol. 2016 13 9 826 836 10.1080/15476286.2016.1197482 27315396
    [Google Scholar]
  42. Wang Z. Li K. Huang W. Long non-coding RNA NEAT1-centric gene regulation. Cell. Mol. Life Sci. 2020 77 19 3769 3779 10.1007/s00018‑020‑03503‑0 32219465
    [Google Scholar]
  43. Huang S. Huang Z. Luo Q. Qing C. The expression of lncRNA NEAT1 in human tuberculosis and its antituberculosis effect. BioMed Res. Int. 2018 2018 1 8 10.1155/2018/9529072 30534569
    [Google Scholar]
  44. Imamura K. Takaya A. Ishida Y. Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs. EMBO J. 2018 37 13 e97723 10.15252/embj.201797723 29880601
    [Google Scholar]
  45. Zhou W. Chen X. Hu Q. Chen X. Chen Y. Huang L. Galectin-3 activates TLR4/NF-κB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. BMC Cancer 2018 18 1 580 10.1186/s12885‑018‑4461‑z
    [Google Scholar]
  46. Liu Z. Lu T. Liu S. Long non coding RNA NEAT1 contributes to lipopolysaccharide induced inflammation and apoptosis of human middle ear epithelial cells via regulating the miR 301b 3p/TLR4 axis. Exp. Ther. Med. 2021 22 6 1360 10.3892/etm.2021.10795 34659506
    [Google Scholar]
  47. An Q. Lu Z. Xie Y. Li Y. Wei H. Cao Y. Knockdown of long non-coding RNA NEAT1 relieves the inflammatory response of spinal cord injury through targeting miR-211-5p/MAPK1 axis. Bioengineered 2021 12 1 2702 2712 10.1080/21655979.2021.1930925 34151707
    [Google Scholar]
  48. Zhang P. Cao L. Zhou R. Yang X. Wu M. The lncRNA Neat1 promotes activation of inflammasomes in macrophages. Nat. Commun. 2019 10 1 1495 10.1038/s41467‑019‑09482‑6 30940803
    [Google Scholar]
  49. Kim J. Lee B. Kim Y. Kim B.C. Kim J.T. Cho H.H. Comprehensive investigation of the expression profiles of common long noncoding RNAs during microglial activation. Genomics Inform. 2023 21 1 e2 10.5808/gi.22061 37037460
    [Google Scholar]
  50. Dong Q. Ren G. Hao D. Assessment of MIR3142HG genetic polymorphisms and the susceptibility of lumbar disc herniation in the Chinese population. Sci. Rep. 2024 14 1 29542 10.1038/s41598‑024‑80758‑8 39604548
    [Google Scholar]
  51. Liu X. Lu Y. Zhu J. A long noncoding RNA, antisense IL-7, promotes inflammatory gene transcription through facilitating histone acetylation and switch/sucrose nonfermentable chromatin remodeling. J. Immunol. 2019 203 6 1548 1559 10.4049/jimmunol.1900256 31383742
    [Google Scholar]
  52. Roux B.T. Heward J.A. Donnelly L.E. Jones S.W. Lindsay M.A. Catalog of differentially expressed long non-coding RNA following activation of human and mouse innate immune response. Front. Immunol. 2017 8 1038 10.3389/fimmu.2017.01038 28900427
    [Google Scholar]
  53. Demirel I. Persson A. Brauner A. Sنrndahl E, Kruse R, Persson K. Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils. Sci. Rep. 2020 10 1 21837 10.1038/s41598‑020‑78651‑1 33318544
    [Google Scholar]
  54. Alshaikh S.A. El-banna T. Sonbol F. Farghali M.H. Correlation between antimicrobial resistance, biofilm formation, and virulence determinants in uropathogenic Escherichia coli from Egyptian hospital. Ann. Clin. Microbiol. Antimicrob. 2024 23 1 20 10.1186/s12941‑024‑00679‑2 38402146
    [Google Scholar]
  55. Kishk R. Bacterial pattern of community-acquired urinary tract infections: A challenge for antimicrobial resistance. Egypt. J. Med. Microbiol. 2021 30 3 153 162 10.51429/EJMM30320
    [Google Scholar]
  56. Tarek A. Abdalla S. Dokmak N.A. Ahmed A.A. El-Mahdy T.S. Safwat N.A. Bacterial diversity and antibiotic resistance patterns of community-acquired urinary tract infections in mega size clinical samples of Egyptian patients: A cross-sectional study. Cureus 2024 16 1 e51838 10.7759/cureus.51838 38327928
    [Google Scholar]
  57. Gutierrez Jauregui R. Fleige H. Bubke A. Rohde M. Weiss S. Fِrster R. IL-1β Promotes Staphylococcus aureus biofilms on implants in vivo. Front. Immunol. 2019 10 1082 10.3389/fimmu.2019.01082 31156635
    [Google Scholar]
  58. Liu H.Y. Prentice E.L. Webber M.A. Mechanisms of antimicrobial resistance in biofilms. NPJ Antimicrob Resist 2024 2 1 27 10.1038/s44259‑024‑00046‑3 39364333
    [Google Scholar]
  59. Long F. Li X. Pan J. The role of lncRNA NEAT1 in human cancer chemoresistance. Cancer Cell Int. 2024 24 1 236 10.1186/s12935‑024‑03426‑x 38970092
    [Google Scholar]
  60. Qu Y. Tan H.Y. Chan Y.T. Jiang H. Wang N. Wang D. The functional role of long noncoding RNA in resistance to anticancer treatment. Ther. Adv. Med. Oncol. 2020 12 1758835920927850 10.1177/1758835920927850 32536982
    [Google Scholar]
  61. Alemi F. Poornajaf Y. Hosseini F. Interaction between lncRNAs and RNA-binding proteins (RBPs) influences DNA damage response in cancer chemoresistance. Mol. Biol. Rep. 2024 51 1 308 10.1007/s11033‑024‑09288‑w 38366290
    [Google Scholar]
  62. Zhang H. Song T. Qin C. Xu H. Qiao M. A novel non-coding RNA CsiR regulates the ciprofloxacin resistance in Proteus vulgaris by interacting with emrB mRNA. Int. J. Mol. Sci. 2021 22 19 10627 10.3390/ijms221910627 34638966
    [Google Scholar]
  63. Gaurav A. Bakht P. Saini M. Pandey S. Pathania R. Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors. Microbiology 2023 169 5 001333 10.1099/mic.0.001333 37224055
    [Google Scholar]
  64. Jin K.T. Lu Z.B. Lv J.Q. Zhang J.G. The role of long non-coding RNAs in mediating chemoresistance by modulating autophagy in cancer. RNA Biol. 2020 17 12 1727 1740 10.1080/15476286.2020.1737787 32129701
    [Google Scholar]
  65. Jasim S.A. Altalbawy F.M.A. Uthirapathy S. Regulation of immune-mediated chemoresistance in cancer by lncRNAs: An in-depth review of signaling pathways. Naunyn Schmiedebergs Arch. Pharmacol. 2025 ••• 1 28 10.1007/s00210‑025‑04081‑3 40202675
    [Google Scholar]
  66. Zheng J. Wang X. Shi J. Expression and clinical significance of lncRNA NEAT1 in patients with spinal tuberculosis. Dis. Markers 2022 2022 1 15 10.1155/2022/5748756 35465262
    [Google Scholar]
  67. Huang Q. Huang C. Luo Y. He F. Zhang R. Circulating lncRNA NEAT1 correlates with increased risk, elevated severity and unfavorable prognosis in sepsis patients. Am. J. Emerg. Med. 2018 36 9 1659 1663 10.1016/j.ajem.2018.06.008 29936011
    [Google Scholar]
  68. Mazurek M. Brzozowska A. Małecka-Massalska T. Powrózek T. Plasma circulating lncRNAs: MALAT1 and NEAT1 as biomarkers of radiation-induced adverse effects in laryngeal cancer patients. Diagnostics 2025 15 6 676 10.3390/diagnostics15060676 40150019
    [Google Scholar]
  69. Zhang R.X. Zhang Z.X. Zhao X.Y. Mechanism of action of lncRNA-NEAT1 in immune diseases. Front. Genet. 2025 16 1501115 10.3389/fgene.2025.1501115 40110044
    [Google Scholar]
  70. Walther K. Schulte L.N. The role of lncRNAs in innate immunity and inflammation. RNA Biol. 2021 18 5 587 603 10.1080/15476286.2020.1845505 33138685
    [Google Scholar]
  71. Gao Y. Li S. Dong R. Li X. Long noncoding RNA MIR3142HG accelerates lipopolysaccharide-induced acute lung injury via miR-95-5p/JAK2 axis. Hum. Cell 2022 35 3 856 870 10.1007/s13577‑022‑00687‑4 35277830
    [Google Scholar]
  72. Lin Y. Leng Q. Zhan M. Jiang F. A plasma long noncoding RNA signature for early detection of lung cancer. Transl. Oncol. 2018 11 5 1225 1231 10.1016/j.tranon.2018.07.016 30098474
    [Google Scholar]
  73. Morlion A Everaert C Nuytens J Hulstaert E Vandesompele J Mestdagh P. Custom long non-coding RNA capture enhances detection sensitivity in different human sample types. RNA Biol 2021 18 sup1 215 22 10.1080/15476286.2021.1971438 34470578
    [Google Scholar]
  74. Hoon D.S. Lessard L. Long Noncoding RNA (LncRNA) as a biomarker and therapeutic marker in cancer United States patent US 9,410,206 2016
    [Google Scholar]
/content/journals/biot/10.2174/0118722083388214250924193840
Loading
/content/journals/biot/10.2174/0118722083388214250924193840
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: UTI ; Long non-coding RNA ; lncRNA ; Bacterial infection ; AMR ; pathogenic E. coli
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test