VIRULENCE FACTORS OF E. COLI, ASSOCIATED WITH URINARY TRACT INFECTIONS

Authors

  • Marina Miroshnikova Medical University Varna Author
  • Denis Niyazi Medical University Varna Author
  • Temenuga Stoeva Medical University Varna Author

DOI:

https://doi.org/10.58395/fr8j7s17

Keywords:

Escherichia coli, urinary tract infections, virulence factors

Abstract

Urinary tract infections (UTIs) are the most common type of infections second only to respiratory tract infections. Millions of UTI cases are reported each year, affecting in- and outpatients. The most frequent causative agents of UTIs are the enteric Gram-negative bacteria, among which Escherichia coli (E. coli) dominates. While most strains of E. coli are harmless and indeed play a beneficial role in gut health, some strains (uropathogenic Escherichia coli, UPEC) can cause infections when they are translocated to generally sterile body areas, such as the urinary tract.

This review presents the wide range of virulence factors of UPEC, involved in the urinary tract colonization, infection development and host tissue invasion. Cell-associated and extracellular key virulence factors such as adhesins, invasins, iron acquisition factors, factors mediating serum resistance, toxins and structural components are discussed in detail. Also, the review focuses on the process of biofilm formation, another crucial virulence factor in UPEC, responsible for UTI persistence, reoccurrence and antimicrobial therapy failure. The regulatory mechanisms involved in biofilm production are also discussed.

Downloads

Download data is not yet available.

References

1. Bonten M, Johnson JR, van den Biggelaar AHJ, Georgalis L, Geurtsen J, de Palacios PI, Gravenstein S, Verstraeten T, Hermans P, Poolman JT. Epidemiology of Escherichia coli Bacteremia: A Systematic Literature Review. Clin Infect Dis. 2021;72(7):1211-1219. https://doi.org/10.1093/cid/ciaa210

2. Baldy-Chudzik K, Bok E, Mazurek J. Znane i nowe warianty patogennych Escherichia coli jako konsekwencja plastycznego genomu [Well-known and new variants of pathogenic Escherichia coli as a consequence of the plastic genome]. Postepy Hig Med Dosw (Online). 2015;69:345-361. Polish. https://doi.org/10.5604/17322693.1145173

3. Dale AP, Woodford N. Extra-intestinal pathogenic Escherichia coli (ExPEC): Disease, carriage and clones. J Infect. 2015;71(6):615-626. https://doi.org/10.1016/j.jinf.2015.09.009

4. Köhler CD, Dobrindt U. What defines extraintestinal pathogenic Escherichia coli? Int J Med Microbiol. 2011;301(8):642-647. https://doi.org/10.1016/j.ijmm.2011.09.006

5. Tivendale KA, Logue CM, Kariyawasam S, Jordan D, Hussein A, Li G, Wannemuehler Y, Nolan LK. Avian-pathogenic Escherichia coli strains are similar to neonatal meningitis E. coli strains and are able to cause meningitis in the rat model of human disease. Infect Immun. 2010;78(8):3412-3419. https://doi.org/10.1128/IAI.00347-10

6. Stamm WE, Norrby SR. Urinary tract infections: disease panorama and challenges. J Infect Dis. 2001;183(Suppl1):S1-S4. https://doi.org/10.1086/318850

7. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002;113(Suppl1A):5S-13S. https://doi.org/10.1016/s0002-9343(02)01054-9

8. Zhou Y, Zhou Z, Zheng L, Gong Z, Li Y, Jin Y, Huang Y, Chi M. Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options. Int J Mol Sci. 2023;24(13):10537. https://doi.org/10.3390/ijms241310537

9. Simpson BW, May JM, Sherman DJ, Kahne D, Ruiz N. Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane. Philos Trans R Soc Lond B Biol Sci. 2015;370(1679):20150029. https://doi.org/10.1098/rstb.2015.0029

10. Fratamico PM, DebRoy C, Liu Y, Needleman DS, Baranzoni GM, Feng P. Advances in Molecular Serotyping and Subtyping of Escherichia coli. Front Microbiol. 2016;7:644. https://doi.org/10.3389/fmicb.2016.00644

11. Abe CM, Salvador FA, Falsetti IN, Vieira MA, Blanco J, Blanco JE, Blanco M, Machado AM, Elias WP, Hernandes RT, Gomes TA. Uropathogenic Escherichia coli (UPEC) strains may carry virulence properties of diarrhoeagenic E. coli. FEMS Immunol Med Microbiol. 2008;52(3):397-406. https://doi.org/10.1111/j.1574-695x.2008.00388.x

12. Yamamoto S. Molecular epidemiology of uropathogenic Escherichia coli. J Infect Chemother. 2007;13(2):68-73. https://doi.org/10.1007/s10156-007-0506-y

13. Paniagua-Contreras GL, Monroy-Pérez E, Rodríguez-Moctezuma JR, Domínguez-Trejo P, Vaca-Paniagua F, Vaca S. Virulence factors, antibiotic resistance phenotypes and O-serogroups of Escherichia coli strains isolated from community-acquired urinary tract infection patients in Mexico. J Microbiol Immunol Infect. 2017;50(4):478-485. https://doi.org/10.1016/j.jmii.2015.08.005

14. Mohammed EJ, Hasan KC, Allami M. Phylogenetic groups, serogroups and virulence factors of uropathogenic Escherichia coli isolated from patients with urinary tract infection in Baghdad, Iraq. Iran J Microbiol. 2022;14(4):445-457. https://doi.org/10.18502/ijm.v14i4.10230

15. Prakapaite R, Saab F, Planciuniene R, Petraitis V, Walsh TJ, Petraitiene R, Semoskaite R, Baneviciene R, Kalediene L, Kavaliauskas P. Molecular Characterization of Uropathogenic Escherichia coli Reveals Emergence of Drug Resistant O15, O22 and O25 Serogroups. Medicina (Kaunas). 2019;55(11):733. https://doi.org/10.3390/medicina55110733

16. Billips BK, Schaeffer AJ, Klumpp DJ. Molecular basis of uropathogenic Escherichia coli evasion of the innate immune response in the bladder. Infection and Immunity. 2008;76(9):3891–3900. https://doi.org/10.1128/IAI.00069-08

17. Hunstad DA, Justice SS, Hung CS, Lauer SR, Hultgren SJ. Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli. Infect Immun. 2005;73(7):3999-4006. https://doi.org/10.1128/iai.73.7.3999-4006.2005

18. Jacobson SH, Ostenson CG, Tullus K, Brauner A. Serum resistance in Escherichia coli strains causing acute pyelonephritis and bacteraemia. APMIS. 1992;100(2):147-153.

19. Reusch RN. Insights into the structure and assembly of Escherichia coli outer membrane protein A. FEBS J. 2012 Mar;279(6):894-909. https://doi.org/10.1111/j.1742-4658.2012.08484.x

20. Nielsen DW, Ricker N, Barbieri NL, Allen HK, Nolan LK, Logue CM. Outer membrane protein A (OmpA) of extraintestinal pathogenic Escherichia coli. BMC Res Notes. 2020;13(1):51. https://doi.org/10.1186/s13104-020-4917-5

21. Nicholson TF, Watts KM, Hunstad DA. OmpA of uropathogenic Escherichia coli promotes postinvasion pathogenesis of cystitis. Infect Immun. 2009;77(12):5245-5251. https://doi.org/10.1128/iai.00670-09

22. Lane MC, Lockatell V, Monterosso G, Lamphier D, Weinert J, Hebel JR, Johnson DE, Mobley HL. Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract. Infect Immun. 2005;73(11):7644-7656. https://doi.org/10.1128/iai.73.11.7644-7656.2005

23. Wright KJ, Seed PC, Hultgren SJ. Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization. Infect Immun. 2005;73(11):7657-7668. https://doi.org/10.1128/iai.73.11.7657-7668.2005

24. Ramesh KU, Nguyen NT, Dewangan NK, Mohiuddin SG, Orman MA, Cirino PC, Conrad JC. Co-Expression of type 1 fimbriae and flagella in Escherichia coli: consequences for adhesion at interfaces. Soft Matter. 2024;20(37):7397-7404. https://doi.org/10.1039/D4SM00499J

25. Simms AN, Mobley HL. PapX, a P fimbrial operon-encoded inhibitor of motility in uropathogenic Escherichia coli. Infect Immun. 2008;76(11):4833-4841. https://doi.org/10.1128/IAI.00630-08

26. Nielubowicz GR, Mobley HL. Host-pathogen interactions in urinary tract infection. Nat Rev Urol. 2010;7(8):430-441. https://doi.org/10.1038/nrurol.2010.101

27. Blanco M, Blanco JE, Rodrı ´guez E, Abalia I, Alonso MP, Blanco J. Detection of virulence genes in uropathogenic Escherichia coli by polymerase chain reaction (PCR): comparison with results obtained using phenotypic methods. J Microbiol Meth. 1997;31:37–43. https://doi.org/10.1016/S0167-7012(97)00087-0

28. Klemm P, Schembri MA. Bacterial adhesins: function and structure. Int J Med Microbiol. 2000;290(1):27-35. https://doi.org/10.1016/s1438-4221(00)80102-2

29. Mancuso G, Midiri A, Gerace E, Marra M, Zummo S, Biondo C. Urinary Tract Infections: The Current Scenario and Future Prospects. Pathogens. 2023;12(4):623. https://doi.org/10.3390/pathogens12040623

30. Vega-Hernández R, Ochoa SA, Valle-Rios R, Jaimes-Ortega GA, Arellano-Galindo J, Aparicio-Ozores G, Ibarra JA, Hernández-Castro R, Cruz-Córdova A, Xicohtencatl-Cortes J. Flagella, Type I Fimbriae and Curli of Uropathogenic Escherichia coli Promote the Release of Proinflammatory Cytokines in a Coculture System. Microorganisms. 2021;9(11):2233. https://doi.org/10.3390/microorganisms9112233

31. Dadi BR, Abebe T, Zhang L, Mihret A, Abebe W, Amogne W. Distribution of virulence genes and phylogenetics of uropathogenic Escherichia coli among urinary tract infection patients in Addis Ababa, Ethiopia. BMC Infect Dis. 2020;20(1):108. https://doi.org/10.1186/s12879-020-4844-z

32. Raeispour M, Ranjbar R. Antibiotic resistance, virulence factors and genotyping of Uropathogenic Escherichia coli strains. Antimicrob Resist Infect Control. 2018;7:118. https://doi.org/10.1186/s13756-018-0411-4

33. Tarchouna M, Ferjani A, Ben-Selma W, Boukadida J. Distribution of uropathogenic virulence genes in Escherichia coli isolated from patients with urinary tract infection. Int J Infect Dis. 2013;17(6):e450-e453. https://doi.org/10.1016/j.ijid.2013.01.025

34. Sarowska J, Futoma-Koloch B, Jama-Kmiecik A, Frej-Madrzak M, Ksiazczyk M, Bugla-Ploskonska G, Choroszy-Krol I. Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports. Gut Pathog. 2019;11:10. https://doi.org/10.1186/s13099-019-0290-0

35. Rahdar M, Rashki A, Miri HR, Rashki Ghalehnoo M. Detection of pap, sfa, afa, foc, and fim Adhesin-Encoding Operons in Uropathogenic Escherichia coli Isolates Collected From Patients With Urinary Tract Infection. Jundishapur J Microbiol. 2015;8(8):e22647. https://doi.org/10.5812/jjm.22647

36. Zamani H, Salehzadeh A. Biofilm formation in uropathogenic Escherichia coli: association with adhesion factor genes. Turk J Med Sci. 2018;48(1):162-167. https://doi.org/10.3906/sag-1707-3

37. Yazdi M, Bouzari M, Ghaemi E A. Detection of fim, pap, sfa and afa Adhesin-Encoding Operons in Escherichia coli Strains Isolated from Urinary Tract Infections. Med Lab J. 2018;12(5):10-15. http://dx.doi.org/10.29252/mlj.12.5.10

38. Nivetha RM, Mariappan S, Sekar U, Aishwarya KVL. Detection of Virulence Determinants of Uropathogenic Escherichia coli. Cureus. 2025;17(2):e79116. https://doi.org/10.7759/cureus.79116

39. Schwan WR. Regulation of fim genes in uropathogenic Escherichia coli. World J Clin Infect Dis. 2011;1(1):17-25. https://doi.org/10.5495/wjcid.v1.i1.17

40. Blomfield IC. The regulation of pap and type 1 fimbriation in Escherichia coli. Adv Microb Physiol. 2001;45:1-49. https://doi.org/10.1016/s0065-2911(01)45001-6

41. Chahales P, Thanassi DG. Structure, Function, and Assembly of Adhesive Organelles by Uropathogenic Bacteria. Microbiol Spectr. 2015;3(5):10.1128/microbiolspec.UTI-0018-2013. https://doi.org/10.1128/microbiolspec.uti-0018-2013

42. Sivick KE, Mobley HL. Waging war against uropathogenic Escherichia coli: winning back the urinary tract. Infect Immun. 2010;78(2):568-585. https://doi.org/10.1128/iai.01000-09

43. Krogfelt KA, Bergmans H, Klemm P. Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae. Infect Immun. 1990;58(6):1995-1998. https://doi.org/10.1128/iai.58.6.1995-1998.1990

44. Schwartz DJ, Kalas V, Pinkner JS, Chen SL, Spaulding CN, Dodson KW, Hultgren SJ. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci U S A. 2013;110(39):15530-15537. https://doi.org/10.1073/pnas.1315203110

45. Melican K, Sandoval RM, Kader A, Josefsson L, Tanner GA, Molitoris BA, Richter-Dahlfors A. Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. PLoS Pathog. 2011;7(2):e1001298. https://doi.org/10.1371/journal.ppat.1001298

46. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J. 2000;19(12):2803-2812. https://doi.org/10.1093/emboj/19.12.2803

47. Wiles TJ, Kulesus RR, Mulvey MA. Origins and virulence mechanisms of uropathogenic Escherichia coli. Exp Mol Pathol. 2008;85(1):11-19. https://doi.org/10.1016/j.yexmp.2008.03.007

48. Lopatto EDB, Santiago-Borges JM, Sanick DA, Malladi SK, Azimzadeh PN, Timm MW, Fox IF, Schmitz AJ, Turner JS, Ahmed SS, Ortinau L, Gualberto NC, Pinkner JS, Dodson KW, Ellebedy AH, Kau AL, Hultgren SJ. Monoclonal antibodies targeting the FimH adhesin protect against uropathogenic E. coli UTI. bioRxiv [Preprint]. 2024;11:2024.12.10.627638. https://doi.org/10.1101/2024.12.10.627638

49. Wright KJ, Hultgren SJ. Sticky fibers and uropathogenesis: bacterial adhesins in the urinary tract. Future Microbiol. 2006;1(1):75-87. https://doi.org/10.2217/17460913.1.1.75

50. Qin X, Hu F, Wu S, Ye X, Zhu D, Zhang Y, Wang M. Comparison of adhesin genes and antimicrobial susceptibilities between uropathogenic and intestinal commensal Escherichia coli strains. PLoS One. 2013;8(4):e61169. https://doi.org/10.1371/journal.pone.0061169

51. Stapleton A. Novel mechanism of P-fimbriated Escherichia coli virulence in pyelonephritis. J Am Soc Nephrol. 2005;16(12):3458-3460. https://doi.org/10.1681/asn.2005101045

52. Mattoo TK, Shaikh N, Nelson CP. Contemporary Management of Urinary Tract Infection in Children. Pediatrics. 2021;147(2):e2020012138. https://doi.org/10.1542/peds.2020-012138

53. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management; Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610. https://doi.org/10.1542/peds.2011-1330

54. Norinder BS, Köves B, Yadav M, Brauner A, Svanborg C. Do Escherichia coli strains causing acute cystitis have a distinct virulence repertoire? Microb Pathog. 2012;52(1):10-16. https://doi.org/10.1016/j.micpath.2011.08.005

55. Källenius G, Möllby R, Svenson SB, Helin I, Hultberg H, Cedergren B, Winberg J. Occurrence of P-fimbriated Escherichia coli in urinary tract infections. Lancet. 1981;2(8260-61):1369-1372. https://doi.org/10.1016/s0140-6736(81)92797-5

56. Zagaglia C, Ammendolia MG, 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. https://doi.org/10.3390/microorganisms10071425

57. Shah C, Baral R, Bartaula B, Shrestha LB. Virulence factors of uropathogenic Escherichia coli (UPEC) and correlation with antimicrobial resistance. BMC Microbiol. 2019;19(1):204. https://doi.org/10.1186/s12866-019-1587-3

58. Lane MC, Mobley HL. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney Int. 2007;72(1):19-25. https://doi.org/10.1038/sj.ki.5002230

59. Salamzade R, McElheny CL, Manson AL, Earl AM, Shaikh N, Doi Y. Genomic epidemiology and antibiotic susceptibility profiling of uropathogenic Escherichia coli among children in the United States. mSphere. 2023;8(5):e0018423. https://doi.org/10.1128/msphere.00184-23

60. Werneburg GT, Thanassi DG. Pili Assembled by the Chaperone/Usher Pathway in Escherichia coli and Salmonella. EcoSal Plus. 2018;8(1):10.1128/ecosalplus.ESP-0007-2017. https://doi.org/10.1128/ecosalplus.esp-0007-2017

61. Behzadi, Payam. Uropathogenic Escherichia Coli and Fimbrial Adhesins Virulome. Urinary Tract Infection - The Result of the Strength of the Pathogen, or the Weakness of the Host, InTech, 2018. https://doi.org/10.5772/intechopen.71374.

62. Balsalobre C, Morschhäuser J, Hacker J, Uhlin BE. Transcriptional analysis of the sfa and pap determinants of uropathogenic Escherichia coli strains. Adv Exp Med Biol. 2000;485:119-122. https://doi.org/10.1007/0-306-46840-9_15

63. Prasadarao NV, Wass CA, Kim KS. Identification and characterization of S fimbria-binding sialoglycoproteins on brain microvascular endothelial cells. Infect Immun. 1997;65(7):2852-2860. https://doi.org/10.1128/iai.65.7.2852-2860.1997

64. Mulvey MA. Adhesion and entry of uropathogenic Escherichia coli. Cell Microbiol. 2002;4(5):257-271.

65. Jacobsen SM, Shirtliff ME. Proteus mirabilis biofilms and catheter-associated urinary tract infections. Virulence. 2011;2(5):460-465. https://doi.org/10.4161/viru.2.5.17783

66. Lasaro MA, Salinger N, Zhang J, Wang Y, Zhong Z, Goulian M, Zhu J. F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917. Appl Environ Microbiol. 2009;75(1):246-251.

67. Subashchandrabose S, Mobley HLT. Virulence and Fitness Determinants of Uropathogenic Escherichia coli. Microbiol Spectr. 2015;3(4):10.1128/microbiolspec.UTI-0015-2012. https://doi.org/10.1128/microbiolspec.uti-0015-2012

68. Wurpel DJ, Totsika M, Allsopp LP, Hartley-Tassell LE, Day CJ, Peters KM, Sarkar S, Ulett GC, Yang J, Tiralongo J, Strugnell RA, Jennings MP, Schembri MA. F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature and recognise Galβ1-3GlcNAc-containing glycans. PLoS One. 2014;9(3):e93177. https://doi.org/10.1371/journal.pone.0093177

69. Alvarez-Fraga L, Phan MD, Goh KGK, Nhu NTK, Hancock SJ, Allsopp LP, Peters KM, Forde BM, Roberts LW, Sullivan MJ, Totsika M, Beatson SA, Ulett GC, Schembri MA. Differential Afa/Dr Fimbriae Expression in the Multidrug-Resistant Escherichia coli ST131 Clone. mBio. 2022;13(1):e0351921. https://doi.org/10.1128/mbio.03519-21

70. 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. https://doi.org/10.3390/microorganisms11092169

71. Nowicki B, Selvarangan R, Nowicki S. Family of Escherichia coli Dr adhesins: decay-accelerating factor receptor recognition and invasiveness. J Infect Dis. 2001;183(Suppl 1):S24-S27. https://doi.org/10.1086/318846

72. Korotkova N, Yarova-Yarovaya Y, Tchesnokova V, Yazvenko N, Carl MA, Stapleton AE, Moseley SL. Escherichia coli DraE adhesin-associated bacterial internalization by epithelial cells is promoted independently by decay-accelerating factor and carcinoembryonic antigen-related cell adhesion molecule binding and does not require the DraD invasin. Infect Immun. 2008;76(9):3869-3880. https://doi.org/10.1128/IAI.00427-08

73. Das M, Hart-Van Tassell A, Urvil PT, Lea S, Pettigrew D, Anderson KL, Samet A, Kur J, Matthews S, Nowicki S, Popov V, Goluszko P, Nowicki BJ. Hydrophilic domain II of Escherichia coli Dr fimbriae facilitates cell invasion. Infect Immun. 2005;73(9):6119-6126. https://doi.org/10.1128/iai.73.9.6119-6126.2005

74. Frömmel U, Lehmann W, Rödiger S, Böhm A, Nitschke J, Weinreich J, Groß J, Roggenbuck D, Zinke O, Ansorge H, Vogel S, Klemm P, Wex T, Schröder C, Wieler LH, Schierack P. Adhesion of human and animal Escherichia coli strains in association with their virulence-associated genes and phylogenetic origins. Appl Environ Microbiol. 2013;79(19):5814-5829. https://doi.org/10.1128/AEM.01384-13

75. Vigil PD, Alteri CJ, Mobley HL. Identification of in vivo-induced antigens including an RTX family exoprotein required for uropathogenic Escherichia coli virulence. Infect Immun. 2011;79(6):2335-2344. https://doi.org/10.1128/IAI.00110-11

76. Vigil PD, Wiles TJ, Engstrom MD, Prasov L, Mulvey MA, Mobley HL. The repeat-in-toxin family member TosA mediates adherence of uropathogenic Escherichia coli and survival during bacteremia. Infect Immun. 2012;80(2):493-505. https://doi.org/10.1128/IAI.05713-11

77. Luterbach CL, Forsyth VS, Engstrom MD, Mobley HLT. TosR-Mediated Regulation of Adhesins and Biofilm Formation in Uropathogenic Escherichia coli. mSphere. 2018;3(3):e00222-18. https://doi.org/10.1128/mSphere.00222-18

78. Arredondo-Alonso S, Blundell-Hunter G, Fu Z, Gladstone RA, Fillol-Salom A, Loraine J, Cloutman-Green E, Johnsen PJ, Samuelsen Ø, Pöntinen AK, Cléon F, Chavez-Bueno S, De la Cruz MA, Ares MA, Vongsouvath M, Chmielarczyk A, Horner C, Klein N, McNally A, Reis JN, Penadés JR, Thomson NR, Corander J, Taylor PW, McCarthy AJ. Evolutionary and functional history of the Escherichia coli K1 capsule. Nat Commun. 2023;14(1):3294. https://doi.org/10.1038/s41467-023-39052-w

79. Bien J, Sokolova O, Bozko P. Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage. Int J Nephrol. 2012;2012:681473. https://doi.org/10.1155/2012/681473

80. Schwan WR, Beck MT, Hultgren SJ, Pinkner J, Woolever NL, Larson T. Down-regulation of the kps region 1 capsular assembly operon following attachment of Escherichia coli type 1 fimbriae to D-mannose receptors. Infect Immun. 2005;73(2):1226-1231. https://doi.org/10.1128/iai.73.2.1226-1231.2005

81. Sora VM, Meroni G, Martino PA, Soggiu A, Bonizzi L, Zecconi A. Extraintestinal Pathogenic Escherichia coli: Virulence Factors and Antibiotic Resistance. Pathogens. 2021;10(11):1355. https://doi.org/10.3390/pathogens10111355

82. Stanley P, Koronakis V, Hughes C. Acylation of Escherichia coli hemolysin: a unique protein lipidation mechanism underlying toxin function. Microbiol Mol Biol Rev. 1998;62(2):309-333. https://doi.org/10.1128/mmbr.62.2.309-333.1998

83. Felmlee T, Pellett S, Welch RA. Nucleotide sequence of an Escherichia coli chromosomal hemolysin. J Bacteriol. 1985;163(1):94-105. https://doi.org/10.1128/jb.163.1.94-105.1985

84. Murase K, Martin P, Porcheron G, Houle S, Helloin E, Pénary M, Nougayrède JP, Dozois CM, Hayashi T, Oswald E. HlyF Produced by Extraintestinal Pathogenic Escherichia coli Is a Virulence Factor That Regulates Outer Membrane Vesicle Biogenesis. J Infect Dis. 2016;213(5):856-865. https://doi.org/10.1093/infdis/jiv506

85. Chagneau CV, Payros D, Goman A, Goursat C, David L, Okuno M, Bordignon PJ, Séguy C, Massip C, Branchu P, Ogura Y, Nougayrède JP, Marenda M, Oswald E. HlyF, an underestimated virulence factor of uropathogenic Escherichia coli. Clin Microbiol Infect. 2023;29(11):1449.e1-1449.e9. https://doi.org/10.1016/j.cmi.2023.07.024

86. David L, Taieb F, Pénary M, Bordignon PJ, Planès R, Bagayoko S, Duplan-Eche V, Meunier E, Oswald E. Outer membrane vesicles produced by pathogenic strains of Escherichia coli block autophagic flux and exacerbate inflammasome activation. Autophagy. 2022;18(12):2913-2925. https://doi.org/10.1080/15548627.2022.2054040

87. Lerm M, Schmidt G, Aktories K. Bacterial protein toxins targeting rho GTPases. FEMS Microbiol Lett. 2000;188(1):1-6. https://doi.org/10.1111/j.1574-6968.2000.tb09159.x

88. Villalonga P, Ridley AJ. Rho GTPases and cell cycle control. Growth Factors. 2006;24(3):159-164. https://doi.org/10.1080/08977190600560651

89. Mao Y, Finnemann SC. Regulation of phagocytosis by Rho GTPases. Small GTPases. 2015;6(2):89-99. https://doi.org/10.4161/21541248.2014.989785

90. Lemonnier M, Landraud L, Lemichez E. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology. FEMS Microbiol Rev. 2007;31(5):515-534. https://doi.org/10.1111/j.1574-6976.2007.00078.x

91. Carlini F, Maroccia Z, Fiorentini C, Travaglione S, Fabbri A. Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review. Int J Mol Sci. 2021;22(22):12610. https://doi.org/10.3390/ijms222212610

92. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-284. https://doi.org/10.1038/nrmicro3432

93. Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda Y, Yoshida O. Distribution of virulence factors in Escherichia coli isolated from urine of cystitis patients. Microbiol Immunol. 1995;39(6):401-404. https://doi.org/10.1111/j.1348-0421.1995.tb02219.x

94. Rippere-Lampe KE, O'Brien AD, Conran R, Lockman HA. Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf(1)) attenuates the virulence of uropathogenic Escherichia coli. Infect Immun. 2001;69(6):3954-3964. https://doi.org/10.1128/iai.69.6.3954-3964.2001

95. Guyer DM, Henderson IR, Nataro JP, Mobley HL. Identification of sat, an autotransporter toxin produced by uropathogenic Escherichia coli. Mol Microbiol. 2000;38(1):53-66. https://doi.org/10.1046/j.1365-2958.2000.02110.x

96. Guyer DM, Radulovic S, Jones FE, Mobley HL. Sat, the secreted autotransporter toxin of uropathogenic Escherichia coli, is a vacuolating cytotoxin for bladder and kidney epithelial cells. Infect Immun. 2002;70:4539–4546. https://doi.org/10.1128/IAI.70.8.4539-4546.2002

97. Cover TL. The vacuolating cytotoxin of Helicobacter pylori. Mol Microbiol. 1996;20(2):241-246. https://doi.org/10.1111/j.1365-2958.1996.tb02612.x

98. Freire CA, Silva RM, Ruiz RC, Pimenta DC, Bryant JA, Henderson IR, Barbosa AS, Elias WP. Secreted Autotransporter Toxin (Sat) Mediates Innate Immune System Evasion. Front Immunol. 2022;13:844878. https://doi.org/10.3389/fimmu.2022.844878

99. Heimer SR, Rasko DA, Lockatell CV, Johnson DE, Mobley HL. Autotransporter genes pic and tsh are associated with Escherichia coli strains that cause acute pyelonephritis and are expressed during urinary tract infection. Infect Immun. 2004;72(1):593-597. https://doi.org/10.1128/iai.72.1.593-597.2004

100. Ganz T. Iron in innate immunity: starve the invaders. Curr Opin Immunol. 2009;21(1):63-67. https://doi.org/10.1016/j.coi.2009.01.011

101. Skaar EP. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog. 2010;6(8):e1000949. https://doi.org/10.1371/journal.ppat.1000949

102. Valdebenito M, Bister B, Reissbrodt R, Hantke K, Winkelmann G. The detection of salmochelin and yersiniabactin in uropathogenic Escherichia coli strains by a novel hydrolysis-fluorescence-detection (HFD) method. Int J Med Microbiol. 2005;295(2):99-107. https://doi.org/10.1016/j.ijmm.2005.02.001

103. Saha R, Saha N, Donofrio RS, Bestervelt LL. Microbial siderophores: a mini review. J Basic Microbiol. 2013 Apr;53(4):303-317. https://doi.org/10.1002/jobm.201100552

104. Nairz M, Dichtl S, Schroll A, Haschka D, Tymoszuk P, Theurl I, Weiss G. Iron and innate antimicrobial immunity-Depriving the pathogen, defending the host. J Trace Elem Med Biol. 2018;48:118-133. https://doi.org/10.1016/j.jtemb.2018.03.007

105. Hood MI, Skaar EP. Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol. 2012;10(8):525-537. https://doi.org/10.1038/nrmicro2836

106. Gao M, Zhao T, Zhang C, Li P, Wang J, Han J, Zhang N, Pang B, Liu S. Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host. Biomed Pharmacother. 2023;163:114859. https://doi.org/10.1016/j.biopha.2023.114859

107. Ratledge C, Dover LG. Iron metabolism in pathogenic bacteria. Annu Rev Microbiol. 2000;54:881-941. https://doi.org/10.1146/annurev.micro.54.1.881

108. Garénaux A, Caza M, Dozois CM. The Ins and Outs of siderophore mediated iron uptake by extra-intestinal pathogenic Escherichia coli. Vet Microbiol. 2011;153(1-2):89-98. https://doi.org/10.1016/j.vetmic.2011.05.023

109. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10(5):1033-1043. https://doi.org/10.1016/s1097-2765(02)00708-6

110. Raffatellu M, George MD, Akiyama Y, Hornsby MJ, Nuccio SP, Paixao TA, Butler BP, Chu H, Santos RL, Berger T, Mak TW, Tsolis RM, Bevins CL, Solnick JV, Dandekar S, Bäumler AJ. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe. 2009;5(5):476-486. https://doi.org/10.1016/j.chom.2009.03.011

111. Usein CR, Damian M, Tatu-Chitoiu D, Capusa C, Fagaras R, Tudorache D, Nica M, Le Bouguénec C. Prevalence of virulence genes in Escherichia coli strains isolated from Romanian adult urinary tract infection cases. J Cell Mol Med. 2001;5(3):303-310. https://doi.org/10.1111/j.1582-4934.2001.tb00164.x

112. Kot B, Wicha J, Grużewska A, Piechota M, Wolska K, Obrębska M. Virulence factors, biofilm-forming ability, and antimicrobial resistance of urinary Escherichia coli strains isolated from hospitalized patients. Turk J Med Sci. 2016;46(6):1908-1914. https://doi.org/10.3906/sag-1508-105

113. Feldmann F, Sorsa LJ, Hildinger K, Schubert S. The salmochelin siderophore receptor IroN contributes to invasion of urothelial cells by extraintestinal pathogenic Escherichia coli in vitro. Infect Immun. 2007;75(6):3183-3187. https://doi.org/10.1128/IAI.00656-06

114. Heffernan JR, Wildenthal JA, Tran H, Katumba GL, McCoy WH, Henderson JP. Yersiniabactin is a quorum-sensing autoinducer and siderophore in uropathogenic Escherichia coli. mBio. 2024;15(2):e0027723. https://doi.org/10.1128/mbio.00277-23

115. Sabri M, Caza M, Proulx J, Lymberopoulos MH, Brée A, Moulin-Schouleur M, Curtiss R 3rd, Dozois CM. Contribution of the SitABCD, MntH, and FeoB metal transporters to the virulence of avian pathogenic Escherichia coli O78 strain chi7122. Infect Immun. 2008;76(2):601-611. https://doi.org/10.1128/iai.00789-07

116. Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, Kádas L, Hedlund KO, Johansson J, Chapman MR, Jacobson SH, Römling U, Agerberth B, Brauner A. Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog. 2010;6(7):e1001010. https://doi.org/10.1371/journal.ppat.1001010

117. Sharma G, Sharma S, Sharma P, Chandola D, Dang S, Gupta S, Gabrani R. Escherichia coli biofilm: development and therapeutic strategies. J Appl Microbiol. 2016;121(2):309-319. https://doi.org/10.1111/jam.13078

118. Ewers C, Li G, Wilking H, Kiessling S, Alt K, Antáo EM, Laturnus C, Diehl I, Glodde S, Homeier T, Böhnke U, Steinrück H, Philipp HC, Wieler LH. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they? Int J Med Microbiol. 2007;297(3):163-176. https://doi.org/10.1016/j.ijmm.2007.01.003

119. Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, Hultgren SJ. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci U S A. 2004;101(5):1333-1338. https://doi.org/10.1073/pnas.0308125100

120. Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, Hultgren SJ. Intracellular bacterial biofilm-like pods in urinary tract infections. Science. 2003;301(5629):105-107. https://doi.org/10.1126/science.1084550

121. Glover M, Moreira CG, Sperandio V, Zimmern P. Recurrent urinary tract infections in healthy and nonpregnant women. Urol Sci. 2014;25(1):1-8. https://doi.org/10.1016/j.urols.2013.11.007

122. Abraham SN, Miao Y. The nature of immune responses to urinary tract infections. Nat Rev Immunol. 2015;15(10):655-663. https://doi.org/10.1038/nri3887

123. Lila ASA, Rajab AAH, Abdallah MH, Rizvi SMD, Moin A, Khafagy ES, Tabrez S, Hegazy WAH. Biofilm Lifestyle in Recurrent Urinary Tract Infections. Life (Basel). 2023;13(1):148. https://doi.org/10.3390/life13010148

124. Ballén V, Cepas V, Ratia C, Gabasa Y, Soto SM. Clinical Escherichia coli: From Biofilm Formation to New Antibiofilm Strategies. Microorganisms. 2022;10(6):1103. https://doi.org/10.3390/microorganisms10061103

125. Rishpana MS, Kabbin JS. Candiduria in Catheter Associated Urinary Tract Infection with Special Reference to Biofilm Production. J Clin Diagn Res. 2015;9(10):DC11-13. https://doi.org/10.7860/jcdr/2015/13910.6690

126. Balestrino D, Souweine B, Charbonnel N, Lautrette A, Aumeran C, Traoré O, Forestier C. Eradication of microorganisms embedded in biofilm by an ethanol-based catheter lock solution. Nephrol Dial Transplant. 2009;24(10):3204-329. https://doi.org/10.1093/ndt/gfp187

127. Niveditha S, Pramodhini S, Umadevi S, Kumar S, Stephen S. The Isolation and the Biofilm Formation of Uropathogens in the Patients with Catheter Associated Urinary Tract Infections (UTIs). J Clin Diagn Res. 2012;6(9):1478-1482. https://doi.org/10.7860/jcdr/2012/4367.2537

128. Gogoi M, Sharma A, Hazarika NK. Biofilm formation by bacterial isolates from patients on indwelling medical devices. Indian J Med Microbiol. 2015;33(2):319-320. https://doi.org/10.4103/0255-0857.154896

129. Srinivasan R, Santhakumari S, Poonguzhali P, Geetha M, Dyavaiah M, Xiangmin L. Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections. Front Microbiol. 2021;12:676458. https://doi.org/10.3389/fmicb.2021.676458

130. Delcaru C, Alexandru I, Podgoreanu P, Grosu M, Stavropoulos E, Chifiriuc MC, Lazar V. Microbial Biofilms in Urinary Tract Infections and Prostatitis: Etiology, Pathogenicity, and Combating strategies. Pathogens. 2016;5(4):65. https://doi.org/10.3390/pathogens5040065

131. Karygianni L, Ren Z, Koo H, Thurnheer T. Biofilm Matrixome: Extracellular Components in Structured Microbial Communities. Trends Microbiol. 2020;28(8):668-681. https://doi.org/10.1016/j.tim.2020.03.016

132. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002;15(2):167-193. https://doi.org/10.1128/cmr.15.2.167-193.2002

133. Solano C, Echeverz M, Lasa I. Biofilm dispersion and quorum sensing. Curr Opin Microbiol. 2014;18:96-104. https://doi.org/10.1016/j.mib.2014.02.008

134. Vidal O, Longin R, Prigent-Combaret C, Dorel C, Hooreman M, Lejeune P. Isolation of an Escherichia coli K-12 mutant strain able to form biofilms on inert surfaces: involvement of a new ompR allele that increases curli expression. J Bacteriol. 1998;180(9):2442-2449. https://doi.org/10.1128/jb.180.9.2442-2449.1998

135. Klemm P, Schembri M. Type 1 Fimbriae, Curli, and Antigen 43: Adhesion, Colonization, and Biofilm Formation. EcoSal Plus. 2004;1(1). https://doi.org/10.1128/ecosalplus.8.3.2.6

136. Laganenka L, Colin R, Sourjik V. Chemotaxis towards autoinducer 2 mediates autoaggregation in Escherichia coli. Nat Commun. 2016;7:12984. https://doi.org/10.1038/ncomms12984

137. Stærk K, Khandige S, Kolmos HJ, Møller-Jensen J, Andersen TE. Uropathogenic Escherichia coli Express Type 1 Fimbriae Only in Surface Adherent Populations Under Physiological Growth Conditions. J Infect Dis. 2016;213(3):386-394. https://doi.org/10.1093/infdis/jiv422

138. Miyazaki J, Ba-Thein W, Kumao T, Obata Yasuoka M, Akaza H, Hayshi H. Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells. FEMS Immunol Med Microbiol. 2002;33(1):23-26. https://doi.org/10.1111/j.1574-695x.2002.tb00567.x

139. Behzadi P. Classical chaperone-usher (CU) adhesive fimbriome: uropathogenic Escherichia coli (UPEC) and urinary tract infections (UTIs). Folia Microbiol (Praha). 2020;65(1):45-65.

140. Bunduki GK, Heinz E, Phiri VS, Noah P, Feasey N, Musaya J. Virulence factors and antimicrobial resistance of uropathogenic Escherichia coli (UPEC) isolated from urinary tract infections: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):753. https://doi.org/10.1186/s12879-021-06435-7

141. Tewawong N, Kowaboot S, Pimainog Y, Watanagul N, Thongmee T, Poovorawan Y. Distribution of phylogenetic groups, adhesin genes, biofilm formation, and antimicrobial resistance of uropathogenic Escherichia coli isolated from hospitalized patients in Thailand. PeerJ. 2020;8:e10453. https://doi.org/10.7717/peerj.10453

142. Wood TK, Knabel SJ, Kwan BW. Bacterial persister cell formation and dormancy. Appl Environ Microbiol. 2013;79(23):7116-7121. https://doi.org/10.1128/AEM.02636-13

143. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010 Sep;8(9):623-633. https://doi.org/10.1038/nrmicro2415

144. Itoh Y, Rice JD, Goller C, Pannuri A, Taylor J, Meisner J, Beveridge TJ, Preston JF 3rd, Romeo T. Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-beta-1,6-N-acetyl-D-glucosamine. J Bacteriol. 2008;190(10):3670-3680. https://doi.org/10.1128/jb.01920-07

145. Wang X, Preston JF 3rd, Romeo T. The pgaABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation. J Bacteriol. 2004;186(9):2724-2734. https://doi.org/10.1128/jb.186.9.2724-2734.2004

146. Serra DO, Richter AM, Hengge R. Cellulose as an architectural element in spatially structured Escherichia coli biofilms. J Bacteriol. 2013;195(24):5540-5554. https://doi.org/10.1128/jb.00946-13

147. Navasa N, Rodríguez-Aparicio L, Martínez-Blanco H, Arcos M, Ferrero MA. Temperature has reciprocal effects on colanic acid and polysialic acid biosynthesis in E. coli K92. Appl Microbiol Biotechnol. 2009;82(4):721-729. https://doi.org/10.1007/s00253-008-1840-4

148. Limoli DH, Jones CJ, Wozniak DJ. Bacterial Extracellular Polysaccharides in Biofilm Formation and Function. Microbiol Spectr. 2015;3(3):10.1128/microbiolspec.MB-0011-2014. https://doi.org/10.1128/microbiolspec.mb-0011-2014

149. Sharma D, Misba L, Khan AU. Antibiotics versus biofilm: an emerging battleground in microbial communities. Antimicrob Resist Infect Control. 2019;8:76. https://doi.org/10.1186/s13756-019-0533-3

150. Vogeleer P, Tremblay YD, Mafu AA, Jacques M, Harel J. Life on the outside: role of biofilms in environmental persistence of Shiga-toxin producing Escherichia coli. Front Microbiol. 2014;5:317. https://doi.org/10.3389/fmicb.2014.00317

151. Ejrnæs K, Stegger M, Reisner A, Ferry S, Monsen T, Holm SE, Lundgren B, Frimodt-Møller N. Characteristics of Escherichia coli causing persistence or relapse of urinary tract infections: phylogenetic groups, virulence factors and biofilm formation. Virulence. 2011;2(6):528-537. https://doi.org/10.4161/viru.2.6.18189

152. Norinder BS, Lüthje P, Yadav M, Kadas L, Fang H, Nord CE, Brauner A. Cellulose and PapG are important for Escherichia coli causing recurrent urinary tract infection in women. Infection. 2011;39(6):571-574. https://doi.org/10.1007/s15010-011-0199-0

153. Salo J, Sevander JJ, Tapiainen T, Ikäheimo I, Pokka T, Koskela M, Uhari M. Biofilm formation by Escherichia coli isolated from patients with urinary tract infections. Clin Nephrol. 2009;71(5):501-507. https://doi.org/10.5414/cnp71501

154. Tapiainen T, Hanni AM, Salo J, Ikäheimo I, Uhari M. Escherichia coli biofilm formation and recurrences of urinary tract infections in children. Eur J Clin Microbiol Infect Dis. 2014;33(1):111-1115. https://doi.org/10.1007/s10096-013-1935-4

155. Beloin C, Roux A, Ghigo JM. Escherichia coli biofilms. Curr Top Microbiol Immunol. 2008;322:249-289. https://doi.org/10.1007/978-3-540-75418-3_12

156. Campoccia D, Montanaro L, Arciola CR. Extracellular DNA (eDNA). A Major Ubiquitous Element of the Bacterial Biofilm Architecture. Int J Mol Sci. 2021;22(16):9100. https://doi.org/10.3390/ijms22169100

157. Goller CC, Romeo T. Environmental influences on biofilm development. Curr Top Microbiol Immunol. 2008;322:37-66. https://doi.org/10.1007/978-3-540-75418-3_3

158. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol. 2004;2(2):95-108. https://doi.org/10.1038/nrmicro821

159. Donlan RM. Biofilm formation: a clinically relevant microbiological process. Clin Infect Dis. 2001;33(8):1387-1392. https://doi.org/10.1086/322972

160. Kostakioti M, Hadjifrangiskou M, Hultgren SJ. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med. 2013;3(4):a010306. https://doi.org/10.1101/cshperspect.a010306

161. Rumbaugh KP, Sauer K. Biofilm dispersion. Nat Rev Microbiol. 2020;18(10):571-586. https://doi.org/10.1038/s41579-020-0385-0

162. Singh S, Datta S, Narayanan KB, Rajnish KN. Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments. J Genet Eng Biotechnol. 2021;19(1):140. https://doi.org/10.1186/s43141-021-00242-y

163. Römling U, Galperin MY, Gomelsky M. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev. 2013;77(1):1-52. https://doi.org/10.1128/mmbr.00043-12

164. Markova JA, Anganova EV, Turskaya AL, Bybin VA, Savilov ED. Regulation of Escherichia coli Biofilm Formation (Review). Appl Biochem Microbiol. 2018;54:1-11. https://doi.org/10.1134/S0003683818010040

165. Prigent-Combaret C, Brombacher E, Vidal O, Ambert A, Lejeune P, Landini P, Dorel C. Complex regulatory network controls initial adhesion and biofilm formation in Escherichia coli via regulation of the csgD gene. J Bacteriol. 2001;183(24):7213-7223. https://doi.org/10.1128/jb.183.24.7213-7223.2001

166. Majdalani N, Gottesman S. The Rcs phosphorelay: a complex signal transduction system. Annu Rev Microbiol. 2005;59:379-405. https://doi.org/10.1146/annurev.micro.59.050405.101230

167. Serra DO, Hengge R. Stress responses go three dimensional - the spatial order of physiological differentiation in bacterial macrocolony biofilms. Environ Microbiol. 2014;16(6):1455-1471. https://doi.org/10.1111/1462-2920.12483

168. Wood TK. Insights on Escherichia coli biofilm formation and inhibition from whole-transcriptome profiling. Environ Microbiol. 2009;11(1):1-15. https://doi.org/10.1111/j.1462-2920.2008.01768.x

169. Daniels R, Vanderleyden J, Michiels J. Quorum sensing and swarming migration in bacteria. FEMS Microbiol Rev. 2004;28(3):261-289. https://doi.org/10.1016/j.femsre.2003.09.004

170. Withers H, Swift S, Williams P. Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria. Curr Opin Microbiol. 2001;4(2):186-193. https://doi.org/10.1016/s1369-5274(00)00187-9

171. Pereira CS, Thompson JA, Xavier KB. AI-2-mediated signalling in bacteria. FEMS Microbiol Rev. 2013;37(2):156-181. https://doi.org/10.1111/j.1574-6976.2012.00345.x

172. Mayer C, Borges A, Flament-Simon SC, Simões M. Quorum sensing architecture network in Escherichia coli virulence and pathogenesis. FEMS Microbiol Rev. 2023;47(4):fuad031. https://doi.org/10.1093/femsre/fuad031

173. Abraham ISV, Palani A, Ramaswamy BR, Shunmugiah KP, Arumugam VR. Antiquorum sensing and antibiofilm potential of Capparis spinosa. Arch Med Res. 2011;42(8):658-668. https://doi.org/10.1016/j.arcmed.2011.12.002

174. Wolska KI, Grudniak AM, Rudnicka Z, Markowska K. Genetic control of bacterial biofilms. J Appl Genet. 2016;57(2):225-238. https://doi.org/10.1007/s13353-015-0309-2

175. Carniol K, Gilmore MS. Signal transduction, quorum-sensing, and extracellular protease activity in Enterococcus faecalis biofilm formation. J Bacteriol. 2004;186(24):8161-8163. https://doi.org/10.1128/JB.186.24.8161-8163.2004

176. Brackman G, Cos P, Maes L, Nelis HJ, Coenye T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob Agents Chemother. 2011;55(6):2655-2661. https://doi.org/10.1128/aac.00045-11

177. Papenfort K, Bassler BL. Quorum sensing signal-response systems in Gram-negative bacteria. Nat Rev Microbiol. 2016;14(9):576-588. https://doi.org/10.1038/nrmicro.2016.89

178. Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. 2012;2(11):a012427. https://doi.org/10.1101/cshperspect.a012427

179. Bottomley MJ, Muraglia E, Bazzo R, Carfì A. Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. J Biol Chem. 2007;282(18):13592-13600. https://doi.org/10.1074/jbc.m700556200

180. Schneider R, Lockatell CV, Johnson D, Belas R. Detection and mutation of a luxS-encoded autoinducer in Proteus mirabilis. Microbiology (Reading). 2002;148(Pt 3):773-782. https://doi.org/10.1099/00221287-148-3-773

181. Rasmussen TB, Givskov M. Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol. 2006;296(2-3):149-161. https://doi.org/10.1016/j.ijmm.2006.02.005

182. Skindersoe ME, Alhede M, Phipps R, Yang L, Jensen PO, Rasmussen TB, Bjarnsholt T, Tolker-Nielsen T, Høiby N, Givskov M. Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2008;52(10):3648-3663. https://doi.org/10.1128/aac.01230-07

183. Michael B, Smith JN, Swift S, Heffron F, Ahmer BM. SdiA of Salmonella enterica is a LuxR homolog that detects mixed microbial communities. J Bacteriol. 2001;183(19):5733-5742. https://doi.org/10.1128/JB.183.19.5733-5742.2001

184. González Barrios AF, Zuo R, Hashimoto Y, Yang L, Bentley WE, Wood TK. Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022). J Bacteriol. 2006;188(1):305-316. https://doi.org/10.1128/jb.188.1.305-316.2006

185. Salinas N, Povolotsky TL, Landau M, Kolodkin-Gal I. Emerging Roles of Functional Bacterial Amyloids in Gene Regulation, Toxicity, and Immunomodulation. Microbiol Mol Biol Rev. 2020;85(1):e00062-20. https://doi.org/10.1128/MMBR.00062-20

186. Rather MA, Gupta K, Mandal M. Microbial biofilm: formation, architecture, antibiotic resistance, and control strategies. Braz J Microbiol. 2021;52(4):1701-1718. https://doi.org/10.1007/s42770-021-00624-x

187. Dincer S, Masume F, Uslu D, Delik A. Antibiotic Resistance in Biofilm. in Bacterial Biofilms; IntechOpen: London, UK; BOD-Books On Demand: Norderstedt, Germany, 2020.

188. Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO. Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem. 2015;7(4):493-512. https://doi.org/10.4155/fmc.15.6

189. Soto SM. Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence. 2013;4(3):223-229. https://doi.org/10.4161/viru.23724

190. Uruén C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J. Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics (Basel). 2020;10(1):3. https://doi.org/10.3390/antibiotics10010003

Downloads

Published

2025-09-15

Issue

Section

Articles

How to Cite

(1)
Miroshnikova, M.; Niyazi, D.; Stoeva, T. VIRULENCE FACTORS OF E. COLI, ASSOCIATED WITH URINARY TRACT INFECTIONS. Probl Infect Parasit Dis 2025, 53 (2), 35-48. https://doi.org/10.58395/fr8j7s17.