Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Benjamin Dedic
Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Andrea C Rodriguez
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Nicole Nischan
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Michelle R Bond
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Marcel Mettlen
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
David C Trudgian
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Andrew Lemoff
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Marianne Quiding-Järbrink
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Bengt Gustavsson
Department of Surgery, University of Gothenburg, Gothenburg, Sweden
Catharina Steentoft
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Henrik Clausen
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Hamid Mirzaei
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Susann Teneberg
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Ulf Yrlid
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera.
