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Vol. 25, No. 6, 2005
Issue release date: November–December 2005

Tamm-Horsfall Protein Acts as a General Host-Defense Factor against Bacterial Cystitis

Raffi H.S. · Bates, Jr. J.M. · Laszik Z. · Kumar S.
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Abstract

Aims: Tamm-Horsfall protein (THP) is urine’s most abundant protein, but its biological function has remained elusive. Recently, THP-deficient (THP–/–) mice were shown to have difficulty clearing Escherichia coli from the urinary bladder. It has remained unclear if interaction between THP and E. coli is specific for E. coli or if THP has a versatile ability to clear a variety of bacteria from the bladder, and act as a broad host-defense mechanism against urinary tract infection (UTI). In this study, we examined the role of THP as a protective factor against UTI caused by bacteria other than E. coli, namely Klebsiella pneumoniae and Staphylococcus saprophyticus by determining if the THP–/– mouse has difficulty clearing these bacteria from its bladder. Methods: THP gene knockout mice were generated by the technique of homologous recombination. K. pneumoniae and S. saprophyticus were introduced transurethrally, in separate experiments, into the bladders of the THP–/– and genetically similar wild-type (THP+/+) mice. Urine was collected at periodic intervals and cultured to quantitate the degree of bacteriuria. Bladders were surgically removed and examined histomorphometrically to determine the intensity of inflammation. Results: Results showed that both with K. pneumoniae and with S. saprophyticus, the THP–/– mice had more severe bacteriuria in comparison with THP+/+ mice. The inflammatory changes in the bladder were also markedly more intense in THP–/– mice with each of the bacterial species. Conclusions: These findings support the hypothesis that THP helps eliminate K. pneumoniae and S. saprophyticus from the urinary tract and acts as a general host-defense factor against UTI.



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References

  1. Foxman B: Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113(suppl 1):5S–13S.

    External Resources

  2. Hooton TM: Pathogenesis of urinary tract infections: an update. J Antimicrob Chemother 2000;46(suppl 1):1–7.
  3. Tamm I, Horsfall F: Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med 1950;74:108–114.
  4. Serafini-Cessi F, Malagolini N, Cavallone D: Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 2003;42:658–676.
  5. Hard K, Van Zadelhoff G, Moonen P, Kamerling JP, Vliegenthart FG: The Asn linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. Novel sulfated and novel N-acetylgalactosamine containing N-linked carbohydrate chains. Eur J Biochem 1992;209:895–915.
  6. Serafini-Cessi F, Dall’Olio F, Malagolini N: High-mannose oligosaccharides from human Tamm-Horsfall glycoprotein. Biosci Rep 1984;4:269–274.
  7. Easton RL, Patankar MS, Clark GF, Morris HR, Dell A: Pregnancy-associated changes in the glycosylation of Tamm-Horsfall protein. Expression of sialyl Lewis(x) sequences on core 2 type O-glycans derived from uromodulin. J Biol Chem 2000;275:21928–21938.
  8. Badgett A, Kumar S: Phylogeny of Tamm-Horsfall protein. Urol Int 1998;61:72–75.
  9. Hession C, Decker JM, Sherblom AP, Kumar S, Yue CC, Mattaliano RJ, Tizard R, Kawashima E, Schmeissner U, Heletky S, Chow EP, Burne CA, Shaw A, Muchmore AV: Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. Science 1987;237:1479–1484.
  10. Orskov I, Orskov F, Birch-Andersen A: Comparison of Escherichia coli fimbrial antigen F7 with type I fimbriae. Infect Immun 1980;27:657–666.
  11. Orskov I, Ferencz A, Orskov F: Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli. Lancet 1980;1:887.
  12. Parkkinen J, Virkola R, Korhonen TK: Identification of factors in human urine that inhibit the binding of Escherichia coli adhesins. Infect Immun 1988;56:2623–2630.
  13. Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR: Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J Biol Chem 2001;276:9924–9930.
  14. Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, Hultgren SJ, Kumar S: Tamm-Horsfall protein knockout mice are more prone to urinary tract infection. Kidney Int 2004;65:791–797.
  15. Mo L, Zhu XH, Huang HY, Shapiro E, Hasty DL, Wu XR: Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1-fimbriated Escherichia coli. Am J Physiol Renal Physiol 2004;286:F795–F802.

    External Resources

  16. Podschun R, Ullmann U: Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998;11:589–603.
  17. Svanborg C, Godaly G: Bacterial virulence in urinary tract infection. Infect Dis Clin North Am 1997;11:513–529.
  18. Babu JP, Abraham SN, Dabbous MK, Beachey EH: Interaction of a 60-kilodalton D-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli. Infect Immun 1986;54:104–108.
  19. Firon N, Ofek I, Sharon N: Carbohydrate-binding sites of the mannose-specific fimbrial lectins of enterobacteria. Infect Immun 1984;43:1088–1090.
  20. Reinhart HH, Obedeanu N, Sobel JD: Quantitation of Tamm-Horsfall protein binding to uropathogenic Escherichia coli and lectins. J Infect Dis 1990;162:1335–1340.
  21. Kil KS, Darouiche RO, Hull RA, Mansouri MD, Musher DM: Identification of a Klebsiella pneumoniae strain associated with nosocomial urinary tract infection. J Clin Microbiol 1997;35:2370–2374.
  22. Fader RC, Davis CP: Effect of piliation on Klebsiella pneumoniae infection in rat bladders. Infect Immun 1980;30:554–561.
  23. Gunnarsson A, Mardh PA, Lundblad A, Svensson S: Oligosaccharide structures mediating agglutination of sheep erythrocytes by Staphylococcus saprophyticus. Infect Immun 1984;45:41–46.
  24. Fujita K, Yokota T, Oguri T, Fujime M, Kitagawa R: In vitro adherence Staphylococcus saprophyticus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus aureus to human ureter. Urol Res 1992;20:399–402.
  25. Jansen B, Beuth J, Ko HL: Evidence for lectin-mediated adherence of S. saprophyticus and P. aeruginosa to polymers. Zentralbl Bakteriol 1990;272:437–442.
  26. Gatermann S, Kretschmar M, Kreft B, Straube E, Schmidt H, Marre R: Adhesion of Staphylococcus saprophyticus to renal tubular epithelial cells is mediated by an N-acetyl-galactosamine-specific structure. Zentralbl Bakteriol 1991;275:358–363.
  27. Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ: Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet 2002;39:882–892.
  28. Devuyst O, Dahan K, Pirson Y: Tamm-Horsfall protein or uromodulin: new ideas about an old molecule. Nephrol Dial Transplant 2005;20:1290–1294.
  29. Bleyer AJ, Hart TC, Shihabi Z, Robins V, Hoyer JR: Mutations in the uromodulin gene decrease urinary excretion of Tamm-Horsfall protein. Kidney Int 2004;66:974–977.


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