title: Presence of terminal N-acetylgalactosamineβ1-4N-acetylglucosamine residues on O-linked oligosaccharides from gastric MUC5AC: involvement in Helicobacter pylori colonization?
abstract: Isolation of MUC5AC mucins from the gastric mucosa from two secretor individuals (one from normal mucosa from a patient with gastric cancer and one from a control) showed different abilities to bind and induce the proliferation of the Helicobacter pylori strain J99. Analysis of the released O-linked oligosaccharides by LC-MS from these individuals showed a very heterogeneous mixture of species from the cancer patient containing both neutral and sialylated structures, whereas the normal sample showed dominating neutral blood group H terminating structures as well as neutral structures containing the di-N-acetyllactosamine (lacdiNAc) unit GalNAcβ1-4GlcNAcβ1- on the C-6 branch of the reducing end GalNAc. The linkage configuration of these epitopes were determined using C-4-specific fragmentation for the GalNAcβ1-4GlcNAcβ1- glycosidic linkage, comparison of the MS(3) fragmentation with standards for linkage configuration and N-acetylhexosamine type as well as exoglycosidase treatment. It was also shown that the lacdiNAc epitope is present in both human and porcine gastric mucins, indicating that this is an epitope preserved between species. We hypothesize that the termination on gastric MUC5AC with lacdiNAc is in competition with complex glycosylation such as the Le(b) and H type 1 as well as complex sialylated structures. These are epitopes known to bind the H. pylori BabA and SabA adhesins.
authors.affiliation: School of Chemistry,  National University of Ireland, Galway,  Ireland.
authors.forename: Diarmuid T
authors.initials: DT
authors.lastname: Kenny
authors.forename: Emma C
authors.initials: EC
authors.lastname: Skoog
authors.forename: Sara K
authors.initials: SK
authors.lastname: Lindén
authors.forename: Weston B
authors.initials: WB
authors.lastname: Struwe
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.forename: Niclas G
authors.initials: NG
authors.lastname: Karlsson
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D018829:Adhesins, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D002853:Chromatography, Liquid; D000939:Epitopes; D005753:Gastric Mucosa / Q000378:metabolism*; D006031:Glycosylation; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055271:Mucin 5AC / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018829:Adhesins, Bacterial; D000939:Epitopes; D055271:Mucin 5AC; D009844:Oligosaccharides; D000117:Acetylglucosamine