Recognition of Blood Group ABH Type 1 Determinants by the FedF Adhesin of F18-fimbriated Escherichia coli*
- Annelies Coddens‡,1,
- Mette Diswall§,
- Jonas Ångström§,
- Michael E. Breimer§,
- Bruno Goddeeris‡¶,
- Eric Cox‡,2 and
- Susann Teneberg∥,3
- ‡Laboratory of Veterinary Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium, the §Department of Surgery, Sahlgrenska University Hospital, Göteborg SE-413 45, Sweden, the ¶Department of Biosystems, Division of Gene Technology, Faculty of Bioscience Engineering, Katholieke Universiteit Leuven, Kasteelpark Arenberg 30, Heverlee B-3001, Belgium, and the ∥Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, P.O. Box 440, University of Gothenburg, Göteborg S-405 30, Sweden
- ↵2 To whom correspondence may be addressed: Tel.: 32-926-473-96; Fax: 32-926-474-96; E-mail: eric.cox{at}UGent.be. 3 To whom correspondence may be addressed: Tel.: 46-31-786-3492; Fax: 46-31-413-190; E-mail: Susann.Teneberg{at}medkem.gu.se.
Abstract
F18-fimbriated Escherichia coli are associated with porcine postweaning diarrhea and edema disease. Adhesion of F18-fimbriated bacteria to the small intestine of susceptible pigs is mediated by the minor fimbrial subunit FedF. However, the target cell receptor for FedF has remained unidentified. Here we report that F18-fimbriated E. coli selectively interact with glycosphingolipids having blood group ABH determinants on type 1 core, and blood group A type 4 heptaglycosylceramide. The minimal binding epitope was identified as the blood group H type 1 determinant (Fucα2Galβ3GlcNAc), while an optimal binding epitope was created by addition of the terminal α3-linked galactose or N-acetylgalactosamine of the blood group B type 1 determinant (Galα3(Fucα2)Galβ3GlcNAc) and the blood group A type 1 determinant (GalNAcα3(Fucα2)-Galβ3GlcNAc). To assess the role of glycosphingolipid recognition by F18-fimbriated E. coli in target tissue adherence, F18-binding glycosphingolipids were isolated from the small intestinal epithelium of blood group O and A pigs and characterized by mass spectrometry and proton NMR. The only glycosphingolipid with F18-binding activity of the blood group O pig was an H type 1 pentaglycosylceramide (Fucα2Galβ3GlcNAc-β3Galβ4Glcβ1Cer). In contrast, the blood group A pig had a number of F18-binding glycosphingolipids, characterized as A type 1 hexaglycosylceramide (GalNAcα3(Fucα2)Galβ3GlcNAcβ3Galβ4Glcβ1Cer), A type 4 heptaglycosylceramide (GalNAcα3(Fucα2)Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), A type 1 octaglycosylceramide (GalNAcα3(Fucα2)Galβ3GlcNAcβ3Galβ3GlcNAcβ3Galβ4Glcβ1Cer), and repetitive A type 1 nonaglycosylceramide (GalNAcα3(Fucα2)Galβ3GalNAcα3-(Fucα2)Galβ3GlcNAcβ3Galβ4Glcβ1Cer). No blood group antigen-carrying glycosphingolipids were recognized by a mutant E. coli strain with deletion of the FedF adhesin, demonstrating that FedF is the structural element mediating binding of F18-fimbriated bacteria to blood group ABH determinants.
Footnotes
-
↵* This work was supported in part by the Swedish Research Council/Medicine (Grant 11612 to S. T. and Grant 12628 to M. E. B.), the Swedish Cancer Foundation (to S. T.), and Magnus Bergvalls Foundation (to S. T.). The UGent and FWO-Flanders (Grants G001305N and 3G038907) are acknowledged for their financial support.
-
↵
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4.
-
↵1 Received a Ph.D. grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders.
- Received October 14, 2008.
- Revision received January 16, 2009.
- The American Society for Biochemistry and Molecular Biology, Inc.
