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Effects of pH on Helicobacter pylori binding to human gastric mucins: Identification of binding to non-MUC5AC mucins

Lindén, Sara LU ; Mahdavi, J; Hedenbro, Jan LU ; Boren, T and Carlstedt, Ingemar LU (2004) In Biochemical Journal 384(2). p.263-270
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mucosal protection, interaction, host-pathogen, Helicobacter pylori, gastric mucin, glycosylation, pH-depenclence
in
Biochemical Journal
volume
384
issue
2
pages
263 - 270
publisher
Portland Press Limited
external identifiers
  • pmid:15260802
  • wos:000225696900006
  • scopus:10644274393
ISSN
0264-6021
DOI
10.1042/BJ20040402
language
English
LU publication?
yes
id
99637820-38f0-4176-a65e-60b3c9fbfe52 (old id 259376)
date added to LUP
2007-10-24 19:14:20
date last changed
2017-07-30 04:25:47
@article{99637820-38f0-4176-a65e-60b3c9fbfe52,
  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.},
  author       = {Lindén, Sara and Mahdavi, J and Hedenbro, Jan and Boren, T and Carlstedt, Ingemar},
  issn         = {0264-6021},
  keyword      = {mucosal protection,interaction,host-pathogen,Helicobacter pylori,gastric mucin,glycosylation,pH-depenclence},
  language     = {eng},
  number       = {2},
  pages        = {263--270},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Effects of pH on Helicobacter pylori binding to human gastric mucins: Identification of binding to non-MUC5AC mucins},
  url          = {http://dx.doi.org/10.1042/BJ20040402},
  volume       = {384},
  year         = {2004},
}