Mikrobiol. Z. 2022; 84(4):40-47.
doi: https://doi.org/10.15407/microbiolj84.04.040

Suggestion of a fimH Inhibitor by a Molecular Docking Method for Escherichia coli
Isolated from Clinical Samples of Patients with UTI

A.A.R. Alnuaimi1, M.S. Alsaeid1, H.M. Abolmaali2

1Medical college at the University of Babylon
Babylon, 51001, Iraq

2College of Pharmacy at the University of Karbala
Karbala, 56001, Iraq

E. coli is one of the most important organisms that cause urinary tract infection (UTI) in more than 95% of patients with UTI. The aim of this study was to search for inhibitors of (fimH) by a docking method using computer programs and websites specialized for this purpose. Methods. This study involved 63 samples with positive E. coli collected from patients with UTI from February 2021 to October 2021 at the Iraqi hospital in Karbala. Full laboratory investigation for E. coli was made to detect FimH and predictsuitable inhibitors. The Fast Identification System VITEK-2, compact DNA extraction system, and PCR Molecular docking were used. Studies of FimH inhibitor for animals were performed as well. Results. FimH was found in most E. coli isolates, namely in 61 (96.82%) of 63 samples. The principle of the experiment is dependent on activated infection on animals with/without feeding with our drug (chamomile), and then the counted E. coli in their urine chamomile appears to be a good FimH inhibitor, with a docking score of -9.4, and to be able to reduce UTI in roughly 50 percent of rats examined. Conclusions. The chamomile was predicted as a suitable inhibitor of (fi mH) and then tested on rats. The results showed its good inhibitory properties.

Keywords: E. coli, molecular docking, FimH, UPEC, urinary tract infection.

Full text

  1. Zalewska-Piątek B, Piątek R. Phage therapy as a novel strategy in the treatment of urinary tract infections caused by E. coli. Antibiotics. 2020; 9(6):304. https://doi.org/10.3390/antibiotics9060304
  2. Terlizzi ME, Gribaudo G, Maff ei ME. UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies. Frontiers in Microbiology. 2017; 8. https://doi.org/10.3389/fmicb.2017.01566
  3. Scribano D, Sarshar M, Prezioso C, Lucarelli M, Angeloni A, Zagaglia C, Palamara AT, Ambrosi C. D-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor induces stable fimh modifications. Molecules. 2020; 25(2):316. https://doi.org/10.3390/molecules25020316
  4. Klein RD, Hultgren SJ. Urinary tract infections: microbial pathogenesis, host—pathogen interactions and new treatment strategies. Nature Reviews Microbiology. 2020; 18(4):211—226. https://doi.org/10.1038/s41579-020-0324-0
  5. Kalas V. Conformational Basis and Small Molecule Antagonists of E. coli Adhesion to the Urinary Tract. Washington University in St. Louis; 2020.
  6. Klemm P, Krogfelt KA. Type 1 fimbriae of Escherichia coli. In: Fimbriae. CRC Press; 2020:9—26. https://doi.org/10.1201/9781003068259-2
  7. Al-Otaibi JS, Mary YS, Th omas R, Kaya S. Detailed electronic structure, physico-chemical properties, excited state properties, virtual bioactivity screening and SERS analysis of three guanine based antiviral drugs valacyclovir HCl hydrate, acyclovir and ganciclovir. Polycyclic Aromatic Compounds. 2020:1—11. https://doi.org/10.1080/10406638.2020.1773876
  8. Sarshar M, Behzadi P, Ambrosi C, Zagaglia C, Palamara AT, Scribano D. FimH and anti-adhesive therapeutics: A disarming strategy against uropathogens. Antibiotics. 2020; 9(7):397. https://doi.org/10.3390/antibiotics9070397
  9. Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. International journal of molecular sciences. 2019; 20(18):4331. https://doi.org/10.3390/ijms20184331
  10. Mashraqi MM, Chaturvedi N, Alam Q, Alshamrani S, Bahnass MM, Ahmad K, Alqosaibi AI, Alnamshan MM, Ahmad SS, Beg MMA, et al. Biocomputational Prediction Approach Targeting FimH by Natural SGLT2 Inhibitors: A Possible Way to Overcome the Uropathogenic Effect of SGLT2 Inhibitor Drugs. Molecules (Basel, Switzerland). 2021; 26(3):582. https://doi.org/10.3390/molecules26030582
  11. Odhar HA, Rayshan AM, Ahjel SW, Hashim AA, Albeer AAMA. Molecular docking enabled updated screening of the matrix protein VP40 from Ebola virus with millions of compounds in the MCULE database for potential inhibitors. Bioinformation. 2019; 15(9):627—632. https://doi.org/10.6026/97320630015627
  12. Lim VT, Hahn DF, Tresadern G, Bayly CI, Mobley DL. Benchmark assessment of molecular geometries and energies from small molecule force fields. F1000Research. 2020; 9. https://doi.org/10.12688/f1000research.27141.1
  13. Berenger F, Kumar A, Zhang KY, Yamanishi Y. Lean-Docking: Exploiting Ligands’ Predicted Docking Scores to Accelerate Molecular Docking. Journal of Chemical Information and Modeling. 2021; 61(5):2341—2352. https://doi.org/10.1021/acs.jcim.0c01452
  14. Akpaka PE, Vaillant A, Wilson C, Jayaratne P. Extended spectrum beta-lactamase (ESBL) produced by gramnegative bacteria in trinidad and tobago. International Journal of Microbiology. 2021. https://doi.org/10.1155/2021/5582755
  15. Rubin BE, Diamond S, Cress BF, Crits-Christoph A, Lou YC, Borges AL, Shivram H, He C, Xu M, Zhou Z. Species- and site-specific genome editing in complex bacterial communities. Nature microbiology. 2022; 7(1):34—47. https://doi.org/10.1038/s41564-021-01014-7
  16. Nurhikmayani R, Daryono BS, Retnaningrum E. The Isolation and molecular identification of antimicrobialproducing Lactic Acid Bacteria from chao, South Sulawesi (Indonesia) fermented fish product. Biodiversitas Journal of Biological Diversity. 2019; 20(4):1063—1068. https://doi.org/10.13057/biodiv/d200418
  17. Chen SP, Wang HH. An engineered Cas-transposon system for programmable and site-directed DNA transpositions. Th e CRISPR journal. 2019; 2(6):376—394. https://doi.org/10.1089/crispr.2019.0030
  18. Menchaca TM, Juárez-Portilla C, Zepeda RC. Past, Present, and Future of Molecular Docking. In: Drug Discovery and Development-New Advances. IntechOpen; 2020.
  19. Al-Okhedi MJI, Najim TM, Al-shammari BFM, Hasan MS, Jead MR. Effects of E. coli Infection on Kidney Function Tests in Experimentally Inoculated Rats. Medico Legal Update. 2020; 20(4):1319—1322. https://doi.org/10.37506/mlu.v20i4.2012
  20. Gupta K, Donnola SB, Sadeghi Z, Lu L, Erokwu BO, Kavran M, Hijaz A, Flask CA. Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis. J Vis Exp. 2017; 125:54649. https://doi.org/10.3791/54649
  21. Kalas V, Hibbing ME, Maddirala AR, Chugani R, Pinkner JS, Mydock-McGrane LK, Conover MS, Janetka JW, Hultgren SJ. Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection. Proceedings of the National Academy of Sciences. 2018; 115(12):E2819—E2828. https://doi.org/10.1073/pnas.1720140115
  22. Hoffman JF, Fan AX, Neuendorf EH, Vergara VB, Kalinich JF. Hydrophobic sand versus metabolic cages: a comparison of urine collection methods for rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science. 2018; 57(1):51—57.
  23. Puay Yen Yap and Dieter Trau TBPL, Singapore: DIRECT E.COLI CELL COUNT AT OD600. Tip Biosystems. 2019; 1.0(an101):1—3.
  24. Ballesteros-Monrreal M, Arenas-Hernández M, Barrios-Villa E, Juarez J, Álvarez-Ainza M, Taboada P, De la Rosa-López R, Bolado-Martínez E, Valencia D. Bacterial Morphotypes as Important Trait for Uropathogenic E. coli Diagnostic; a Virulence-Phenotype-Phylogeny Study. Microorganisms. 2021; 9: 2381. Virulence Factors and Antibiotic Resistance of Enterobacterales. 2021:19. https://doi.org/10.3390/microorganisms9112381
  25. Aljebory IS, Mohammad KA. Molecular Detection of Some Virulence Genes of Escherichia coli Isolated from UTI Patients in Kirkuk City, Iraq. Journal of Global Pharma Technology. 2019; 11(03):349—355.
  26. Hanafy NA, El-Kemary MA. Silymarin/curcumin loaded albumin nanoparticles coated by chitosan as muco-inhalable delivery system observing anti-inflammatory and anti-COVID-19 characterizations in oleic acid triggered lung injury and in vitro COVID-19 experiment. International Journal of Biological Macromolecules. 2022; 198:101—110. https://doi.org/10.1016/j.ijbiomac.2021.12.073
  27. Akour A, Abuloha S, Mulakhudair AR, Kasabri V, Ala’a B. Complementary and alternative medicine for urinary tract illnesses: A cross-sectional survey in Jordan. Complementary Therapies in Clinical Practice. 2021; 43:101321. https://doi.org/10.1016/j.ctcp.2021.101321
  28. Behzadi P. Classical chaperone-usher (CU) adhesive fimbriome: uropathogenic Escherichia coli (UPEC) and urinary tract infections (UTIs). Folia microbiologica. 2020; 65(1):45—65. https://doi.org/10.1007/s12223-019-00719-x
  29. Di Venanzio G, Flores-Mireles AL, Calix JJ, Haurat MF, Scott NE, Palmer LD, Potter RF, Hibbing ME, Friedman  L, Wang B. Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes. Nature communications. 2019; 10(1):1—13. https://doi.org/10.1038/s41467-019-10706-y
  30. Shukla G, Subrahmanyam C, Khess AS, Kumar CS. CYSTOCRAN Tablet: A Natural Antibiotic Safeguard in Urinary Tract Infections. Mediterranean Journal of Basic and Applied Sciences (MJBAS). 2021; 5(2):71—80. https://doi.org/10.46382/MJBAS.2021.5204
  31. Khan AS, Kniep B, Oelschlaeger TA, Van Die I, Korhonen T, Hacker J. Receptor structure for F1C fimbriae of uropathogenic Escherichia coli. Infect Immun. 2000; 68(6):3541—3547. https://doi.org/10.1128/IAI.68.6.3541-3547.2000
  32. Porru D, Parmigiani A, Tinelli C, Barletta D, Choussos D, Di Franco C, Bobbi V, Bassi S, Miller O, Gardella B, et al. Oral D-mannose in recurrent urinary tract infections in women: a pilot study. Journal of Clinical Urology. 2014; 7(3):208—213. https://doi.org/10.1177/2051415813518332
  33. Touaibia M, Krammer E-M, Shiao TC, Yamakawa N, Wang Q, Glinschert A, Papadopoulos A, Mousavifar L, Maes E, Oscarson S, et al. Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin. Molecules. 2017; 22(7):1101. https://doi.org/10.3390/molecules22071101
  34. Murugan NA, Podobas A, Gadioli D, Vitali E, Palermo G, Markidis S. A Review on Parallel Virtual Screening Soft wares for High-Performance Computers. Pharmaceuticals. 2022; 15(1):63. https://doi.org/10.3390/ph15010063
  35. Heinrich M, Williamson EM, Gibbons S, Barnes J, Prieto-Garcia J. Fundamentals of pharmacognosy and phytotherapy E-BOOK: Elsevier Health Sciences; 2017.
  36. Gomes MN, Muratov EN, Pereira M, Peixoto JC, Rosseto LP, Cravo PV, Andrade CH, Neves BJ. Chalcone derivatives: promising starting points for drug design. Molecules. 2017; 22(8):1210. https://doi.org/10.3390/molecules22081210
  37. Francoeur PG, Masuda T, Sunseri J, Jia A, Iovanisci RB, Snyder I, Koes DR. Three-dimensional convolutional neural networks and a cross-docked data set for structure-based drug design. Journal of Chemical Information and Modeling. 2020; 60(9):4200—4215. https://doi.org/10.1021/acs.jcim.0c00411
  38. Qiu Y, Li X, He X, Pu J, Zhang J, Lu S. Computational methods-guided design of modulators targeting proteinprotein interactions (PPIs). European Journal of Medicinal Chemistry. 2020:112764. https://doi.org/10.1016/j.ejmech.2020.112764
  39. Fatriansyah JF, Rizqillah RK, Yandi MY, Fadilah, Sahlan M. Molecular docking and dynamics studies on propolis sulabiroin-A as a potential inhibitor of SARS-CoV-2. J King Saud Univ Sci. 2022, 34(1):101707—101707. https://doi.org/10.1016/j.jksus.2021.101707