Strain- and blood group-dependent binding of Helicobacter pylori to human gastric MUC5AC glycoforms.
OBJECTIVE
In the stomach, Helicobacter pylori is found both in the mucus layer and adhering to the gastric epithelium. The aim of this study is to characterize the binding of H. pylori to human gastric mucins.


METHODS
H. pylori strains that bind the Lewis(b) (Le(b)) structure (via the BabA adhesin) and/or sialylated structures, along with isogenic adhesion deletion mutants, were used to identify microbe-binding mucins. Gastric mucins from 5 healthy individuals, isolated by density-gradient centrifugation, were investigated for H. pylori binding at neutral pH using a microtiter-based technique.


RESULTS
H. pylori strains that express the BabA adhesins were shown to bind to the MUC5AC mucin in individuals expressing the Le(b) antigen. Further fractionation with an ion-exchange chromatography revealed Le(b)-positive MUC5AC glycoforms that differed in their receptor properties for different H. pylori strains. None of the H. pylori strains studied bound to mucins from Le(b)-negative individuals. However, all strains bound to low-density, nonmucin, Le(b)-negative material on top of the gradients.


CONCLUSIONS
Binding of H. pylori to human gastric MUC5AC isolated from healthy individuals is BabA dependent and mediated by the Le(b) structure presented by the mucin. However, the BabA adhesins demonstrate strain-dependent preference in binding to MUC5AC glycoforms substituted with Le(b), allowing for great interindividual variability in host-microbe interactions.
Lindén
Sara
S
Mucosal Biology Group, Department of Cell and Molecular Biology, Lund University, Sweden.
Nordman
Henrik
H
Hedenbro
Jan
J
Hurtig
Marina
M
Borén
Thomas
T
Carlstedt
Ingemar
I
D018829:Adhesins, Bacterial; D000328:Adult; D001789:Blood Group Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007519:Isoantigens / Q000032:analysis; D007983:Lewis Blood Group Antigens; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000302:isolation & purification / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D013045:Species Specificity; D013270:Stomach / Q000737:chemistry
D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D001789:Blood Group Antigens; D002352:Carrier Proteins; D007519:Isoantigens; D007983:Lewis Blood Group Antigens; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D020033:Protein Isoforms