Abstract

Physiologically, urine and the urinary tract are maintained sterile because of physical and chemical properties of urine and the innate immune system’s action. The urinary tract is constantly exposed to the invasion of microorganisms from the exterior environment, also because of the anatomical placement of the urethra, in the vicinity of the rectum. Particularly vulnerable to urinary tract infections (UTI) are women (an additional risk factor is pregnancy), but also the elderly and children. The main pathogens causing UTI are bacteria; in 70-95% of cases it is the bacterium Escherichia coli. Infections caused by viruses and fungi are less common and are associated with decreased immunity, pharmacotherapy, or some diseases. Bacteria have evolved a number of factors that facilitate the colonization of the urinary tract: the cover and cell membrane antigens O and K1, lipopolysaccharide (LPS), fimbriae, pile and cilia. On the other hand, the human organism has evolved mechanisms to hinder colonization of the urinary tract: mechanisms arising from the anatomical structure of the urinary tract, the physicochemical properties of the urine and the activity of the innate immune system, also known as non-specific, which isolates and destroys pathogens using immunological processes, and the mechanisms for release of antimicrobial substances such as Tamm-Horsfall protein, mucopolysaccharides, immunoglobulins IgA and IgG, lactoferrin, lipocalin, neutrophils, cytokines and antimicrobial peptides. This review aims to analyze the state of knowledge on the mechanisms to maintain the sterility of the urinary tract used by the human organism and bacterial virulence factors to facilitate the colonization of the urinary tract.

References

• 1. Agarwal J., Srivastava S., Singh M.: Pathogenomics of uropathogenicEscherichia coli. Indian J. Med. Microbiol., 2012; 30: 141-149
  Google Scholar
• 2. Apodaca G.: The uroepithelium: not just a passive barrier. Traffic,2004; 5: 117-128
  Google Scholar
• 3. Arcidiacono S., Butler M.M., Mello C.M.: A rapid selective extractionprocedure for the outer membrane protein (OmpF) from Escherichiacoli. Protein Expr. Purif., 2002; 25: 134-137
  Google Scholar
• 4. Belardelli F., Ferrantini M.: Cytokines as a link between innate andadaptive antitumor immunity. Trends Immunol., 2002; 23: 201-208
  Google Scholar
• 5. Ben Mkaddem S., Chassin C., Vandewalle A.: Contribution of renaltubule epithelial cells in the innate immune response during renalbacterial infections and ischemia-reperfusion injury. Chang GungMed. J., 2010; 33: 225-240 6 Beveridge T.J.: Ultrastructure, chemistry, and function of thebacterial wall. Int. Rev. Cytol., 1981; 72: 229-317
  Google Scholar
• 6. (Suppl. 1): S13
  Google Scholar
• 7. Carlsson S., Wiklund N.P., Engstrand L., Weitzberg E., LundbergJ.O.: Effects of pH, nitrite, and ascorbic acid on nonenzymatic nitricoxide generation and bacterial growth in urine. Nitric Oxide,2001; 5: 580-586
  Google Scholar
• 8. Chen S.L., Jackson S.L., Boyko E.J.: Diabetes mellitus and urinarytract infection: epidemiology, pathogenesis and proposed studies inanimal models. J. Urol., 2009; 182 (Suppl. 6): S51-S56
  Google Scholar
• 9. Christmas T.J.: Lymphocyte sub-populations in the bladder wallin normal bladder, bacterial cystitis and interstitial cystitis. Br. J.Urol., 1994; 73: 508-515
  Google Scholar
• 10. Chromek M., Brauner A.: Antimicrobial mechanisms of the urinarytract. J. Mol. Med., 2008; 86: 37-47
  Google Scholar
• 11. Connell H., Agace W., Klemm P., Schembri M., Marild S., SvanborgC.: Type 1 fimbrial expression enhances Escherichia coli virulencefor the urinary tract. Proc. Natl. Acad. Sci. USA, 1996; 93: 9827-9832
  Google Scholar
• 12. Cross A.S., Kim K.S., Wright D.C., Sadoff J.C., Gemski P.: Role of lipopolysaccharideand capsule in the serum resistance of bacteremicstrains of Escherichia coli. J. Infect. Dis., 1986; 154: 497-503
  Google Scholar
• 13. Czekalski S.: Zakażenie układu moczowego – ostre, nawracające,przewlekłe, powikłane. Przew. Lek., 2010; 2: 46-53
  Google Scholar
• 14. Dale B.A., Tao R., Kimball J.R., Jurevic R.J.: Oral antimicrobialpeptides and biological control of caries. BMC Oral Health, 2006;
  Google Scholar
• 15. Duguid J.P., Anderson E.S.: Terminology of bacterial fimbriae,or pili, and their types. Nature, 1967; 215: 89-90
  Google Scholar
• 16. Fair W.R., Couch J., Wehner N.: Prostatic antibacterial factor.Identity and significance. Urology, 1976; 7: 169-177
  Google Scholar
• 17. Foxman B.: Epidemiology of urinary tract infections: incidence,morbidity, and economic costs. Am. J. Med., 2002; 113 (Suppl. 1A): 5S-13S
  Google Scholar
• 18. García-Montoya I.A., Cendón T.S., Arévalo-Gallegos S., RascónCruzQ.: Lactoferrin a multiple bioactive protein: an overview. Biochim.Biophys. Acta, 2012; 1820: 226-236
  Google Scholar
• 19. Hooton T.M., Bradley S.F., Cardenas D.D., Colgan R., GeerlingsS.E., Rice J.C., Saint S., Schaeffer A.J., Tambayh P.A., Tenke P., NicolleL.E.: Diagnosis, prevention, and treatment of catheter-associatedurinary tract infection in adults: 2009 International Clinical PracticeGuidelines from the Infectious Diseases Society of America. Clin.Infect. Dis., 2010; 50: 625-663
  Google Scholar
• 20. Hryniewicz W., Grzesiowski P., Mészáros J., Radzikowski A., OzorowskiT.: Zakażenia układu moczowego. Etiologia, rozpoznawanie, leczenie.wyd. 2, Fundacja Centrum Mikrobiologii Klinicznej, Warszawa 2001
  Google Scholar
• 21. Johnson J.R.: Virulence factors in Escherichia coli urinary tractinfection. Clin. Microbiol. Rev., 1991; 4: 80-128
  Google Scholar
• 22. Kelleher S.L., McCormick N.H., Velasquez V., Lopez V.: Zinc inspecialized secretory tissues: roles in the pancreas, prostate, andmammary gland. Adv. Nutr., 2011; 2: 101-111
  Google Scholar
• 23. Kim J., Kim D.S., Lee Y.S., Choi N.G.: Fungal urinary tract infectionin burn patients with long-term foley catheterization. KoreanJ. Urol., 2011; 52: 626-631
  Google Scholar
• 24. Klonowska-Szymczyk A., Wolska A., Robak E.: Udział receptorówTLR w procesach autoimmunologicznych. Postępy Hig. Med.Dośw., 2009; 63: 331-339
  Google Scholar
• 25. Koch A.L.: The biophysics of the gram-negative periplasmicspace. Crit. Rev. Microbiol., 1998; 24: 23-59
  Google Scholar
• 26. Krcmery S., Dubrava M., Krcmery V.Jr.: Fungal urinary tractinfections in patients at risk. Int. J. Antimicrob. Agents, 1999; 11:289-291
  Google Scholar
• 27. Legrand D., Pierce A., Elass E., Carpentier M., Mariller C., MazurierJ.: Lactoferrin structure and functions. Adv. Exp. Med. Biol.,2008; 606: 163-194
  Google Scholar
• 28. Liu L., Zhao C., Heng H.H., Ganz T.: The human β-defensin-1 andα-defensins are encoded by adjacent genes: two peptide familieswith differing disulfide topology share a common ancestry. Genomics,1997; 43: 316-320
  Google Scholar
• 29. Miano R., Germani S., Vespasiani G.: Stones and urinary tractinfections. Urol. Int., 2007; 79 (Suppl. 1): 32-36
  Google Scholar
• 30. Mierzchała M., Lipińska-Gediga M., Durek G.: The role of LBP intransduction of signal induced by LPS and in modulation of immunesystem response. Adv. Clin. Exp. Med., 2006; 15: 127-134
  Google Scholar
• 31. Müller C.M., Dobrindt U., Nagy G., Emödy L., Uhlin B.E., HackerJ.: Role of histone-like proteins H-NS and StpA in expression of virulencedeterminants of uropathogenic Escherichia coli. J. Bacteriol.,2006; 188: 5428-5438
  Google Scholar
• 32. Mysorekar I.U., Mulvey M.A., Hultgren S.J., Gordon J.I.: Molecularregulation of urothelial renewal and host defenses duringinfection with uropathogenic Escherichia coli. J. Biol. Chem., 2002;277: 7412-7419
  Google Scholar
• 33. Nowicki B., Sledzinska A., Samet A., Nowicki S.: Pathogenesis ofgestational urinary tract infection: urinary obstruction versus immuneadaptation and microbial virulence. BJOG, 2011; 118: 109-112
  Google Scholar
• 34. Oliveira F.A., Paludo K.S., Arend L.N., Farah S.M., Pedrosa F.O.,Souza E.M., Surek M., Picheth G., Fadel-Picheth C.M.: Virulence characteristicsand antimicrobial susceptibility of uropathogenic Escherichiacoli strains. Genet. Mol. Res., 2011; 10: 4114-4125
  Google Scholar
• 35. Ong C.L., Ulett G.C., Mabbett A.N., Beatson S.A., Webb R.I.,Monaghan W., Nimmo G.R., Looke D.F., McEwan A.G., Schembri M.A.:Identification of type 3 fimbriae in uropathogenic Escherichia coli revealsa role in biofilm formation. J. Bacteriol., 2008; 190: 1054-1063
  Google Scholar
• 36. Paduch D.A.: Viral lower urinary tract infections. Curr. Urol.Rep., 2007; 8: 324-335
  Google Scholar
• 37. Parsons C.L., Stein P., Zupkas P., Chenoweth M., Argade S.P.,Proctor J.G., Datta A., Trotter R.N.: Defective Tamm-Horsfall proteinin patients with interstitial cystitis. J. Urol., 2007; 178: 2665-2670
  Google Scholar
• 38. Pastuszka A., Ziółko E., Kuczmik W., Marniok B., Ślusarczyk K.,Lubas T.: Śluzówkowy układ odpornościowy w układzie moczowo–płciowym. Urol. Pol., 2007; 60: 3
  Google Scholar
• 39. Peeling R.W., Brunham R.C.: Chlamydiae as pathogens: new speciesand new issues. Emerg. Infect. Dis., 1996; 2: 307-319
  Google Scholar
• 40. Prakash J.: The kidney in pregnancy: a journey of three decades.Indian J. Nephrol., 2012; 22: 159-167
  Google Scholar
• 41. Przybyła J., Sosnowski M.: Ostre i przewlekłe zakażenie drógmoczowych – diagnostyka i leczenie. Przew. Lek., 2008; 4: 71-77
  Google Scholar
• 42. Radek K., Gallo R.: Antimicrobial peptides: natural effectors ofthe innate immune system. Semin. Immunopathol., 2007; 29: 27-43
  Google Scholar
• 43. Reinhart H.H., Sobel J.D.: The role of Tamm-Horsfall proteinin the pathogenesis of urinary tract infection. Int. Urogynecol. J.,1992; 3: 191-196
  Google Scholar
• 44. Rietschel E.T., Kirikae T., Schade F.U., Mamat U., Schmidt G.,Loppnow H., Ulmer A.J., Zahringer U., Seydel U., Di Padova F., SchreierM., Brade H.: Bacterial endotoxin: molecular relationships ofstructure to activity and function. FASEB J., 1994; 8: 217-225
  Google Scholar
• 45. Roberts J.A., Marklund B.I., Ilver D., Haslam D., Kaack M.B.,Baskin G., Louis M., Möllby R., Winberg J., Normark S.: The Gal(α1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed forpyelonephritis to occur in the normal urinary tract. Proc. Natl. Acad.Sci. USA, 1994; 91: 11889-11893
  Google Scholar
• 46. Ronald A., Ludwig E.: Urinary tract infections in adults withdiabetes. Int. J. Antimicrob. Agents, 2001; 17: 287-292
  Google Scholar
• 47. Schoor R.A., Anderson B., Klumpp D.J., Schaeffer A.J.: SecretoryIGA differentially promotes adherence of type 1-piliated Escherichia colito immortalized vaginal epithelial cell lines. Urology, 2001; 57: 556-561
  Google Scholar
• 48. Shihabi Z.K., Hinsdale M.E., Bleyer A.J.: Analysis of Tamm-Horsfallprotein by high-performance liquid chromatography with nativefluorescence.J. Chromatogr. A, 2004; 1027: 161-166
  Google Scholar
• 49. Shortliffe L.M., McCue J.D.: Urinary tract infections at the ageextremes: pediatrics and geriatrics. Am. J. Med., 2002; 113 (Suppl.1A): 55S-66S
  Google Scholar
• 50. Sikorska-Siudek K.: Rozpoznawanie i leczenie ostrych zakażeńukładu moczowego w praktyce lekarza rodzinnego. Med. Rodzinna,2004; 7: 291-296
  Google Scholar
• 51. Spencer J.D., Hains D.S., Porter E., Bevins C.L., DiRosario J.,Becknell B., Wang H., Schwaderer A.L.: Human alpha defensin 5expression in the human kidney and urinary tract. PLoS One, 2012;7: e31712
  Google Scholar
• 52. Striker R., Nilsson U., Stonecipher A., Magnusson G., HultgrenS.J.: Structural requirements for the glycolipid receptor ofhuman uropathogenic Escherichia coli. Mol. Microbiol., 1995;16: 1021-1029
  Google Scholar
• 53. Świrska J., Matuszek B., Paszkowski T., Nowakowski A.: Powikłaniaokresu okołooperacyjnego z uwzględnieniem ich patogenezyu pacjentów chorych na cukrzycę. Prz. Menopauz., 2011; 15: 316-323
  Google Scholar
• 54. Tolkoff-Rubin N.E., Cotran R.S., Rubin R.H.: Urinary tract infection,pyelonephritis, and reflux nephropathy. W: Brenner B.M.,red. Brenner & Rector’s The Kidney. 8th ed. Vol. 2. Philadelphia:Saunders 2008
  Google Scholar
• 55. Uehling D.T., Johnson D.B., Hopkins W.J.: The urinary tract responseto entry of pathogens. World. J. Urol., 1999; 17: 351-358
  Google Scholar
• 56. van Berkel P.H., van Veen H.A., Geerts M.E., Nuijens J.H.: Characterizationof monoclonal antibodies against human lactoferrin. J.Immunol. Methods, 2002; 267: 139-150
  Google Scholar
• 57. Weichhart T., Haidinger M., Hörl W.H., Säemann M.D.: Currentconcepts of molecular defence mechanisms operative during urinarytract infection. Eur. J. Clin. Invest., 2008; 38 (Suppl. 2): 29-38
  Google Scholar
• 58. Williams G., Fletcher J.T., Alexander S.I., Craig J.C.: Vesicoureteralreflux. J. Am. Soc. Nephrol., 2008; 19: 847-862
  Google Scholar
• 59. Wong E.S., Fennell C.L., Stamm W.E.: Urinary tract infectionamong women attending a clinic for sexually transmitted diseases.Sex. Transm. Dis., 1984; 11: 18-23
  Google Scholar
• 60. Yona-Nadler C., Umanski T., Aizawa S., Friedberg D., RosenshineI.: Integration host factor (IHF) mediates repression of flagella inenteropathogenic and enterohaemorrhagic Escherichia coli. Microbiology,2003; 149: 877-884
  Google Scholar
• 61. Zasloff M.: Antimicrobial peptides, innate immunity, and thenormally sterile urinary tract. J. Am. Soc. Nephrol., 2007; 18: 2810-2816
  Google Scholar
• 62. Zhang D., Zhang G., Hayden M.S., Greenblatt M.B., Bussey C.,Flavell R.A., Ghosh S.: A toll-like receptor that prevents infectionby uropathogenic bacteria. Science, 2004; 303: 1522-1526
  Google Scholar

Full text