Recognition of Blood Group ABH Type 1 Determinants by the FedF Adhesin of F18-fimbriated Escherichia coli

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 (Fuc␣2Gal␤3GlcNAc), while an optimal binding epitope was created by addition of the terminal ␣3-linked galactose or N-acetylgalactosamine of the blood group B type 1 determinant (Gal␣3(Fuc␣2)Gal␤3GlcNAc) and the blood group A type 1 determinant (GalNAc␣3(Fuc␣2)-Gal␤3GlcNAc). 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 (Fuc␣2Gal␤3GlcNAc-␤3Gal␤4Glc␤1Cer). In contrast, the blood group A pig had a number of F18-binding glycosphingolipids, characterized as A type 1 hexaglycosylceramide (GalNAc␣3(Fuc␣2)Gal␤3Glc-NAc␤3Gal␤4Glc␤1Cer), A type 4 heptaglycosylceramide (GalNAc␣3(Fuc␣2)Gal␤3GalNAc␤3Gal␣4Gal␤4Glc␤1Cer), A type 1 octaglycosylceramide (GalNAc␣3(Fuc␣2)Gal␤3GlcNAc␤3-Gal␤3GlcNAc␤3Gal␤4Glc␤1Cer), and repetitive A type 1 nonaglycosylceramide (GalNAc␣3(Fuc␣2)Gal␤3GalNAc␣3-(Fuc␣2)Gal␤3GlcNAc␤3Gal␤4Glc␤1Cer). 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. Enterotoxigenic (ETEC)4 and verotoxigenic Escherichia coli are important causes of disease in man and animal (1, 2). In newly weaned pigs, F18-fimbriated E. coli producing enteroand/or Shiga-like toxins induce diarrhea and/or edema disease, which accounts for substantial economical losses in the pig industry (3). Two virulence factors are of major importance, namely the F18 fimbriae, the adhesive polymeric protein surface appendages of F18-fimbriated E. coli, and the Shiga-like toxin (SLT-IIv), or enterotoxins (STa or STb), that are produced by the bacterium. F18 fimbriae are expressed by the fed (fimbriae associated with edema disease) gene cluster, with fedA encoding the major subunit, fedB the outer membrane usher, fedC the periplasmic chaperone, whereas fedE and fedF encode minor subunits (4). FedF is the adhesive subunit and is presumably located at the tip of the fimbrial structure (5, 6). Typically, tip adhesins consist of two domains: an N-terminal carbohydrate-specific lectin domain and a C-terminal pilin domain (7), which needs to be donor-strand-complemented ...

Differential expression of FUT1 and FUT2 in Large White, Meishan, and Sutai porcine breeds

“…However, Coddens et al (2009) observed that the E. coli F18 receptor is a type 1 H antigen catalyzed by a2-fucosyltransferase that is encoded by FUT2 as opposed to a type 2 H antigen catalyzed by a1-fucosyltransferase that is encoded by FUT1, and Moonens et al (2012) and Lonardi et al (2013) validated these results. Additionally, FUT1 glycosyltransferase converts type 1 H precursors into type 1 H blood group antigens (Kyprianou et al, 1990;Liu et al, 1998;Mathieu et al, 2004).…”

“…In this study, the piglet specimens had been weaned for 1 week, and weaned piglets are very susceptible to E. coli F18 infections at this age (35 days old). The E. coli F18 receptor is a type 1 H antigen of the ABO blood group and a glycosphingolipid derivative (Coddens et al, 2009). Studies reported that ABH blood group antigens were primarily synthesized by the globo-and lactose-series of glycosphingolipid biosynthetic pathways (Hakomori, 2000).…”

“…Studies showed that the E. coli F18 receptor determinant is a type 1 H antigen of the ABH blood group (Coddens et al, 2009). The ABH blood group antigen is a glycosphingolipid on the plasmalemma of red blood cells, and the ABH blood group is determined by the types of sugars present in the glycosphingolipid.…”

Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenicEscherichia coliinfection

“…This test was performed as described by Coddens et al (27); more details are in SI Materials and Methods.…”

Escherichia coliand the mucosal immune system

“…This work examined the specificity of the FedF adhesin tip through structural and site-directed mutagenesis studies. A region for binding to ABH blood group glycans associated with pig enterocytes was defined [5]. Significantly, another region of FedF was identified that interacts with glycosphingolipids and was proposed to be required for initial interactions with lipid bilayers.…”