title: Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins.
abstract: Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.
authors.affiliation: Mucosal Biology Group, Department of Cell and Molecular Biology, BMC/C13, Lund University, SE-22184 Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindén
authors.forename: Jafar
authors.initials: J
authors.lastname: Mahdavi
authors.forename: Jan
authors.initials: J
authors.lastname: Hedenbro
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
authors.forename: Ingemar
authors.initials: I
authors.lastname: Carlstedt
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D002499:Centrifugation, Density Gradient / Q000379:methods; D045604:Extracellular Fluid / Q000737:chemistry / Q000382:microbiology; D005752:Gastric Mucins / Q000737:chemistry / Q000378:metabolism*; D005753:Gastric Mucosa / Q000737:chemistry / Q000382:microbiology; D006031:Glycosylation; D016481:Helicobacter Infections / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*
chemical_list: D005752:Gastric Mucins; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins