Structural requirements for the glycolipid receptor of human uropathogenic Escherichia coli
Robert Striker
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Search for more papers by this authorUlf Nilsson
Organic Chemistry 2, Chemical Centre, The Lund Institute of Technology, University of Lund, PO Box 124, S-221 00 Lund, Sweden.
Search for more papers by this authorAndrea Stonecipher
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Search for more papers by this authorGöran Magnusson
Organic Chemistry 2, Chemical Centre, The Lund Institute of Technology, University of Lund, PO Box 124, S-221 00 Lund, Sweden.
Search for more papers by this authorCorresponding Author
Scott J. Hultgren
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
*For correspondence. Tel. (314)362 6772; Fax (314) 362 1998.Search for more papers by this authorRobert Striker
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Search for more papers by this authorUlf Nilsson
Organic Chemistry 2, Chemical Centre, The Lund Institute of Technology, University of Lund, PO Box 124, S-221 00 Lund, Sweden.
Search for more papers by this authorAndrea Stonecipher
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Search for more papers by this authorGöran Magnusson
Organic Chemistry 2, Chemical Centre, The Lund Institute of Technology, University of Lund, PO Box 124, S-221 00 Lund, Sweden.
Search for more papers by this authorCorresponding Author
Scott J. Hultgren
Department of Molecular Microbiology, Box 8230, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
*For correspondence. Tel. (314)362 6772; Fax (314) 362 1998.Search for more papers by this authorSummary
The binding of uropathogenic Escherichia coli to the globo series of glycolipids via P pili is a critical step in the infectious process that is mediated by a human-specific PapG adhesin. Three classes of PapG adhesins exist with different binding specificities to Galα4Gal-containing glycolipids. The structural basis for PapG recognition of the human glycolipid receptor globoside was investigated by using soluble saccharide analogues as inhibitors of bacterial haemagglutination. The minimum binding epitope was confirmed as the Galα4Gal moiety, but parts of the GalNAcβ and glucose residues, which flank the Galα4Gal in globoside (GbO4), were also shown to be important for strong binding. Furthermore, the same five hydroxyl groups of Galα4Gal in globotriasyl ceramide that were recognized by a previously characterized PapG variant were also recognized by the human-specific PapG in binding the GbO4 that dominates In the human kidney. Saccharide analogues that blocked haemagglutination also blocked the adherence of human uropathogenic E. coli to human kidney sections. Knowledge of the molecular details of the PapG-GbO4 interaction will make it possible to design antiadherence therapeutics.
References
- Beachey, E.H. (1981) Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surfaces. J Inf Dis 143: 325–345.
- Borén, T., Falk, P., Roth, K.A., Larson, G., and Normark, S. (1993) Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 262: 1892–1895.
- Brown, K.E., Anderson, S.M., and Young, N.S. (1993) Erythrocyte P antigen: cellular receptor for B19 parvo-virus. Science 262: 114–116.
-
van Die, I.,
Hoekstra, W., and
Bergmans, H. (1983) Studies on the fimbriae of an Escherichia coli 06:K2:H1:F7 strain: molecular cloning of a DNA fragment encoding a fimbrial antigen responsible for mannose-resistant hemaggluttination of human erythrocytes.
FEMS Microbiol Lett
19: 77–82.
10.1111/j.1574-6968.1983.tb00514.x Google Scholar
- Falk, P., Roth, K.A., Borén, T., Westblom, T.U., Gordon, J.I., and Normark, S. (1993) An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage-specific tropism in the human gastric epithelium. Proc Natl Acad Sci USA 90: 2035–2039.
- Fersht, A.R., J.-P. S., Knill-Jones, J., Lowe, D.M., Wilkinson, A.J., Blow, D.M., Brick, P., Carter, P., Waye, M.M.Y., and Winter, G. (1985) Hydrogen bonding and biological specificity analysed by protein engineering. Nature 314: 235–238.
- Garegg, P., and Oscarsson, S. (1985) Synthesis of 6- and 6′-deoxy derivatives of methyl 4-O-α-d-galatopyranosyl-β-d-galactopyranoside for studies of inhibition of pyelonephritogenic fimbriated E. coli adhesion to urinary epithelium-cell surfaces. Carbohydr Res 137: 270–275.
- Grönberg, G., Nilsson, U., Bock, K., and Magnusson, G. (1994) Nuclear magnetic resonance and conformational investigations of the pentasaccharide of the Forssman antigen and the overlapping di-, tri-, and tetra-saccharide sequence. Carbohydr Res 257: 35–54.
- Haataja, S., Tikkanen, K., Liukkonen, J., Francois-Gerard, C., and Finne, J. (1993) Characterization of a novel bacterial adhesion specificty of Streptococcus suis recognizing blood group P receptor oligosaccharides. J Biol Chem 268: 4311–4317.
- Hultgren, S.J., Normark, S., and Abraham, S.N. (1991) Chaperone-assisted assembly and molecular architecture of adhesive pili. Annu Rev Microbiol 45: 383–415.
- Hultgren, S.J., Abraham, S.N., Caparon, M., Falk, P., III, St Geme, J.W., and Normark, S. (1993) Pilus and non-pilus bacterial adhesins: assembly and function in cell recognition. Cell 73: 887–901.
- Jansson, K., Ahlfors, S., Frejd, T., Kihiberg, J., Magnusson, G., Dahman, J., Noori, G., and Stenvall, K. (1988) 2-(Trimethylsilyl)ethyl glycosides. Synthesis, anomeric deblocking, and transformation into 1,2-trans 1-O-acyl sugars. J Org Chem 53: 5629–5647.
- Johanson, I., Lindstedt, R., and Svanborg, C. (1992) Roles of the pap- and prs-encoded adhesins in Escherichia coli adherence to human uroepithelial cells. Infect Immun 60: 3416–3422.
- Kihlberg, J., Frejd, T., Jansson, K., and Magnusson, G. (1986) Synthetic receptor analogues: preparation of the 3-O-methyl, 3-C-methyl and 3-deoxy derivatives of 4-O-α-d-galactopyranosyl-β-d-galactopyranoside (methyl β-d-galabioside). Carbohydr Res 152: 113–130.
- Kihlberg, J., Frejd, T., Jansson, K., Sundin, A., and Magnusson, G. (1988) Synthetic receptor analogues: preparation and calculated conformations of the 2-deoxy, 6-O-methyl, 6-deoxy and 6-deoxy-6-fluoro derivatives of methyl 4-O-α-d-galactopyranoside (methyl β-d-galabioside) Carbohydr Res 176, 271–286.
- Kihlberg, J., Hultgren, S.J., Normark, S., and Magnusson, G. (1989a) Probing of the combining site of the PapG adhesion of uropathogenic Escherichia coli bacteria by synthetic analogues of galabiose. J Am Chem Soc 111: 6364–6368.
- Kihlberg, J., Frejd, T., Jannson, K., Sundin, A., and Magnusson, G. (1989b) Preparation and calculated conformations of the 2′-, 3′ 4′- and 6′-deoxy, 3′-O-methyl, 4′-epi, and 4′- and 6′-deoxy flouro deriviatives of 4-O-α-d-galactopyranosyl-β-d-galactopyranoside (methyl β-d-galabioside). Carbohydr Res 185: 171–190.
- Leffler, H., and Svanborg-Eden, C. (1980) Chemical identification of a glycosphingolipid receptor for Escherichia coli attaching to human urinary tract epithelial cells and agglutinating human erythrocytes. FEMS Microbiol Lett 8: 127–134.
- Lindberg, A.A., Brown, J.E., Stromberg, N., Westling-Ryd, M., Schultz, J.E., and Karlsson, K.A. (1987) Identification of the carbohydrate receptor for the Shiga toxin produced by Shigella dysentersae Type 1*. J Biol Chem 262: 1779–1785.
- Lindberg, F.P., Lund, B., and Normark, S. (1984) Genes of pyelonephritogenic E. coli required for digalactoside-specific agglutination of human cells. EMBO J 3: 1167–1173.
- Lingwood, C.A., Law, H., Richardson, S., Petric, M., Brunton, J.L., Degrandis, S., and Karmali, M. (1987) Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro. J Biol Chem 262: 8834–8839.
- Lund, B., Marklund, B.I., Stromberg, N., Lindberg, F., Karlsson, K.A., and Normark, S. (1988) Uropathogenic Escherichia coli can express serologically identical pili of different receptor binding specificities. Mol Microbiol 2: 255–263.
-
Magnussen, G.,
Kihlberg, J., and
Hultgren, S.J. (1995) Specificity-mapping of bacterial lectins by inhibition of hemaggluttination using deoxy- and deoxyfluoro analogues of receptor-active saccharides.
Meth Enzymol, in press.
10.1016/S0076-6879(95)53012-6 Google Scholar
- Marklund, B.I., Tennent, J.M., Garcia, E., Hamers, A., Baga, M., Lindberg, F., Gaastra, W., and Normark, S. (1992) Horizontal gene transfer of the Escherichia coli pap and prs pili operons as a mechanism for the development of tissue-specific adhesive properties. Mol Microbiol 6: 2225–2242.
- Neu, H.C. (1992) The crisis in antibiotic resistance. Science 257: 1064–1073.
- Nilsson, U., Ray, A.K., and Magnusson, G. (1994a) Synthesis of the globotetraose and terminal tri-, and di-saccharide fragments. Carbohydr Res 252: 117–136.
- Nilsson, U., Ray, A.K., and Magnusson, G. (1994b) Synthesis of the Forssman pentasacchraide and terminal tetra-, tri-, and di-saccharide fragments. Carbohydr Res 252: 137–148.
- Nilsson, U., Wendler, A., and Magnusson, G. (1994c) Synthesis of the 2′-hydroxy, 4′-deoxy, and 4′ epi analogues of β-d-GalNAc-(1–3)-α-d-Gal-(1–4)-β-d-Gal, the terminal trisaccharide of globotetraose. Acta Chem Scand 48: 356–361.
- Orskov, I., Ferencz, A., and Orskov, F. (1960) Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli. Lancet 1: 887.
- Pressman, D., and Grossberg, A.L. (1968) The Structural Basis of Antibody Specificity. W.A. Benjamin (ed.). New York , pp. 16–29.
- Roberts, J.A., Suarez, G.M., Kaack, M.B., Domingue, G.J., and Svenson, S.B. (1986) Host-parasite relationships in acute pyelonephritis. Am J Kidney Dis 8: 139–145.
- Stromberg, N., Marklund, B.I., Lund, B., Ilver, D., Hamers, A., Gaastra, W., Karlsson, K.A., and Normark, S. (1990) Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Galα1–4Gal-containing isoreceptors. EMBO J 9: 2001–2010.
- Stromberg, N., Nyholm, P.-G., Pascher, I., and Normark, S. (1991) Saccharide orientation at the cell surface affects glycolipid receptor function. Proc Natl Acad Sci USA 88: 9340–9344.
- Svenson, G., Albertson, J., Svenson, C., Magnussen, G., and Dahmen, J. (1986) X-ray crystal structure of galabiose, O-α-d-Galactopyranosyl-(1–4)-d-galactopyranose. J Carbohydr Res 146: 29–38.
- Weis, W., Brown, J.H., Cusack, S., Paulson, J.C., Skehel, J.J., and Wiley, D.C. (1988) Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 333: 426–431.
- Xu, Z., Jones, C.H., Haslam, D., Pinkner, J.S., Dodson, K., Kihlberg, J., and Hultgren, S.J. (1995) Molecular dissection of PapD interaction with PapG reveals two chaperone-binding sites. Mol Microbiol 16: 1011–1020.
Citing Literature
