Skip to content
naulon

No retraction, correction or concern found when last checked on Nov 2, 2026.

The affinity of the FimH fimbrial adhesin is receptor‐driven and quasi‐independent of Escherichia coli pathotypes

Julie Bouckaert, Jenny Mackenzie, José L. De Paz and 11 more

Molecular Microbiology · 2006

doi:10.1111/j.1365-2958.2006.05352.x

Abstract

Summary Type‐1 fimbriae are important virulence factors for the establishment of Escherichia coli urinary tract infections. Bacterial adhesion to the high‐mannosylated uroplakin Ia glycoprotein receptors of bladder epithelium is mediated by the FimH adhesin. Previous studies have attributed differences in mannose‐sensitive adhesion phenotypes between faecal and uropathogenic E. coli to sequence variation in the FimH receptor‐binding domain. We find that FimH variants from uropathogenic, faecal and enterohaemorrhagic isolates express the same specificities and affinities for high‐mannose structures. The only exceptions are FimHs from O157 strains that carry a mutation (Asn135Lys) in the mannose‐binding pocket that abolishes all binding. A high‐mannose microarray shows that all substructures are bound by FimH and that the largest oligomannose is not necessarily the best binder. Affinity measurements demonstrate a strong preference towards oligomannosides exposing Manα1‐3Man at their non‐reducing end. Binding is further enhanced by the β1‐4‐linkage to GlcNAc, where binding is 100‐fold better than that of α‐ d ‐mannose. Manα1‐3Manβ1‐4GlcNAc, a major oligosaccharide present in the urine of α‐mannosidosis patients, thus constitutes a well‐defined FimH epitope. Differences in affinities for high‐mannose structures are at least 10‐fold larger than differences in numbers of adherent bacteria between faecal and uropathogenic strains. Our results imply that the carbohydrate expression profile of targeted host tissues and of natural inhibitors in urine, such as Tamm‐Horsfall protein, are stronger determinants of adhesion than FimH variation.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 56

  1. 1.

    Abraham SN, Sun D, Dale JB, Beachey EH. Conservation of the d-mannose-adhesion protein among type 1 fimbriated members of the family Enterobactericeae. Nature. 1988;336:682-684.

    Not in our library10.1038/336682a0

  2. 2.

    Adams EW, Ratner DM, Bokesch HR, McMahon JB, O'Keefe BR, Seeberger PH. Oligosaccharide and glycoprotein microarrays as tools in HIV glycobiology: glycan-dependent gp120/protein interactions. Chem Biol. 2004;11:875-881.

    Not in our library10.1016/j.chembiol.2004.04.010

  3. 3.

    Aronson M, Medalia O, Schori L, Mirelman D, Sharon N, Ofek I. Prevention of colonization of the urinary-tract by blocking bacterial adherence with methyl-α-d-mannopyranoside. Isr J Med Sci. 1979;15:88.

    Not in our library10.1093/infdis/139.3.329

  4. 4.

    Barnhart MM, Sauer FG, Pinkner JS, Hultgren SJ. Chaperone-subunit-usher interactions required for donor strand exchange during bacterial pilus assembly. J Bacteriol. 2003;185:2723-2730.

    Not in our library10.1128/jb.185.9.2723-2730.2003

  5. 5.

    Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, et al. Tamm-Horsfall protein knockout mice are more prone to urinary tract infection. Kidney Int. 2004;65:791-797.

    Not in our library10.1111/j.1523-1755.2004.00452.x

  6. 6.

    Berglund J, Knight SD. Structural basis for bacterial adhesion in the urinary tract. Adv Exp Med Biol. 2003;535:33-52.

    Not in our library10.1007/978-1-4615-0065-0_3

  7. 7.

    Blahna MT, Zalewski CA, Reuer J, Kahlmeter G, Foxman B, Marrs CF. The role of horizontal gene transfer in the spread of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and Canada. J Antimicrob Chemother. 2006;57:666-672.

    Not in our library10.1093/jac/dkl020

  8. 8.

    Bouckaert J, Berglund J, Schembri M, De Genst E, Cools L, Wuhrer M, et al. Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol Microbiol. 2005;55:441-455.

    Not in our library10.1111/j.1365-2958.2004.04415.x

  9. 9.

    Cavallone D, Malagolini N, Monti A, Wu XR, Serafini-Cessi F. Variation of high mannose chains of Tamm-Horsfall glycoprotein confers differential binding to type 1-fimbriated Escherichia coli. J Biol Chem. 2004;279:216-222.

    Not in our library10.1074/jbc.m308821200

  10. 10.

    Devuyst O, Dahan K, Pirson Y. Tamm-Horsfall protein or uromodulin: new ideas about an old molecule. Nephrol Dial Transplant. 2005;20:1290-1294.

    Not in our library10.1093/ndt/gfh851

  11. 11.

    Duncan MJ, Mann EL, Cohen MS, Ofek I, Sharon N, Abraham SN. The distinct binding specificities exhibited by enterobacterial type 1 fimbriae are determined by their fimbrial shafts. J Biol Chem. 2005;280:37707-37716.

    Not in our library10.1074/jbc.m501249200

  12. 12.

    Durand G, Seta N. Protein glycosylation and diseases: blood and urinary oligosaccharides as markers for diagnosis and therapeutic monitoring. Clin Chem. 2000;46:795-805.

    Not in our library

  13. 13.

    Firon N, Ofek I, Sharon N. Interaction of mannose-containing oligosaccharides with the fimbrial lectin of Escherichia coli. Biochem Biophys Res Commun. 1982;105:1426-1432.

    Not in our library10.1016/0006-291x(82)90947-0

  14. 14.

    Firon N, Ofek I, Sharon N. Carbohydrate specificity of the surface lectins of Escherichia coli, Klebsiella pneumoniae and Salmonella typhimurium. Carbohydr Res. 1983;120:235-249.

    Not in our library10.1016/0008-6215(83)88019-7

  15. 15.

    Firon N, Ofek I, Sharon N. Carbohydrate-binding sites of the mannose-specific fimbrial lectins of enterobacteria. Infect Immun. 1984;43:1088-1090.

    Not in our library10.1128/iai.43.3.1088-1090.1984

  16. 16.

    Geerlings SE, Meiland R, van Lith EC, Brouwer EC, Gaastra W, Hoepelman AI.M. Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells - more in diabetic women than in control subjects. Diabetes Care. 2002;25:1405-1409.

    Not in our library10.2337/diacare.25.8.1405

  17. 17.

    Hoepelman AI.M, Meiland R, Geerlings SE. Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus. Int J Antimicrob Agents. 2003;22:S35-S43.

    Not in our library10.1016/s0924-8579(03)00234-6

  18. 18.

    Hogan MC, Gloor JM, Uhl JR, Cockerill FR, Milliner DS. Two cases of non-O157:H7 Escherichia coli hemolytic uremic syndrome caused by urinary tract infection. Am J Kidney Dis. 2001;38:1-6.

    Not in our library10.1053/ajkd.2001.27731

  19. 19.

    Hung C-S, Bouckaert J, Hung DL, Pinkner J, Winberg C, Defusco A, et al. Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection. Mol Microbiol. 2002;44:903-915.

    Not in our library10.1046/j.1365-2958.2002.02915.x

  20. 20.

    Jones TA, Zou JY, Cowan SW, Kjeldgaard M. Improved methods for building protein models in electron desity maps and the location of errors in these models. Acta Crystallogr. 1991;A47:110-119.

    Not in our library10.1107/s0108767390010224

  21. 21.

    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 USA. 2004;101:1333-1338.

    Not in our library10.1073/pnas.0308125100

  22. 22.

    Kau AL, Hunstad DA, Hultgren SJ. Interaction of uropathogenic Escherichia coli with host uroepithelium. Curr Opin Microbiol. 2005;8:54-59.

    Not in our library10.1016/j.mib.2004.12.001

  23. 23.

    Langermann S, Palaszynski S, Barnhart M, Auguste G, Pinkner JS, Burlein J, et al. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science. 1997;276:607-611.

    Not in our library10.1126/science.276.5312.607

  24. 24.

    McCormick BA, Franklin DP, Laux DC, Cohen PS. Type 1 pili are not necessary for colonization of the streptomycin-treated mouse large intestine by type 1-piliated Escherichia coli F-18 and E. coli K-12. Infect Immun. 1989;57:3022-3029.

    Not in our library10.1128/iai.57.10.3022-3029.1989

  25. 25.

    Madison B, Ofek I, Clegg S, Abraham SN. Type 1 fimbrial shafts of Escherichia coli and Klebsiella pneumoniae influence sugar-binding specificities of their FimH adhesins. Infect Immun. 1994;62:843-848.

    Not in our library10.1128/iai.62.3.843-848.1994

  26. 26.

    Minion FC, Abraham SN, Beachey EH, Goguen JD. The genetic determinant of adhesive function in type 1 fimbriae of Escherichia coli is distinct from the gene encoding the fimbrial subunit. J Bacteriol. 1989;165:1033-1036.

    Not in our library10.1128/jb.165.3.1033-1036.1986

  27. 27.

    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.

    Not in our library10.1152/ajprenal.00357.2003

  28. 28.

    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19:1639-1662.

    Not in our library

  29. 29.

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

    Not in our library10.1046/j.1462-5822.2002.00193.x

  30. 30.

    Nayal M, Hitz BC, Honig B. GRASS: a server for the graphical representation and analysis of structures. Prot Sci. 1999;8:676-679.

    Not in our library10.1110/ps.8.3.676

  31. 31.

    Neeser JR, Koellreutter B, Wuersch P. Oligomannoside-type glycopeptides inhibiting adhesion of Escherichia coli strains mediated by type 1 pili: preparation of potent inhibitors from plant glycoproteins. Infect Immun. 1986;52:428-436.

    Not in our library10.1128/iai.52.2.428-436.1986

  32. 32.

    Norden NE, Lundblad A, Svensson S, Ockerman PA, Autio S. Mannose-containing trisaccharide isolated from urines of 3 patients with mannosidosis. J Biol Chem. 1973;248:6210-6215.

    Not in our library

  33. 33.

    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.

    Not in our library10.1074/jbc.m008610200

  34. 34.

    Pouttu R, Puustinen T, Virkola R, Hacker J, Klemm P, Korhonen TK. Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis-associated Escherichia coli to collagens. Mol Microbiol. 1999;31:1747-1757.

    Not in our library10.1046/j.1365-2958.1999.01311.x

  35. 35.

    Ratner DM, Plante OJ, Seeberger PH. A linear synthesis of branched high-mannose oligosaccharides from the HIV-1 viral surface envelope glycoprotein gp120. Eur J Org Chem. 2002;2002:826-833.

    Not in our library

  36. 36.

    Ratner DM, Adams EW, Su J, O'Keefe BR, Mrksich M, Seeberger PH. Probing protein-carbohydrate interactions with microarrays of synthetic oligosaccharides. Chembiochem. 2004;5:379-382.

    Not in our library10.1002/cbic.200300804

  37. 37.

    Rockendorf N, Sperling O, Lindhorst TK. Trivalent cluster mannosides with aromatic partial structure as ligands for the type 1 fimbrial lectin of Escherichia coli. Austr J Chem. 2002;55:87-93.

    Not in our library

  38. 38.

    van Rooijen JJ.M, Voskamp AF, Kamerling JP, Vliegenthart JF.G. Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein. Glycobiology. 1999;9:21-30.

    Not in our library10.1093/glycob/9.1.21

  39. 39.

    Rosenstein IJ, Stoll MS, Mizuochi T, Childs RA, Hounsell EF, Feizi T. New type of adhesive specificity revealed by oligosaccharide probes in Escherichia-coli from patients with urinary-tract infection. Lancet. 1988;2:1327-1330.

    Not in our library10.1016/s0140-6736(88)90868-9

  40. 40.

    Sanner MF, Olson AJ, Spehner JC. Reduced surface: an efficient way to compute molecular surfaces. Biopolymers. 1996;38:305-320.

    Not in our library10.1002/(sici)1097-0282(199603)38:3<305::aid-bip4>3.0.co;2-y

All 56 references

Cited by papers we hold 2

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.