Acid-dependent adherence of Helicobacter pylori urease to diverse polysaccharides.
OBJECTIVE
The significance of acid-primed recognition of ligands by Helicobacter pylori urease is unknown. This study aimed to further characterize the specificity of urease adherence in vitro and verify whether specific inhibition will translate into in vivo suppression of colonization.


METHODS
A highly sensitive competitive enzyme-linked ligand capture assay was used to quantify the capacity of each test inhibitor to compete with labeled mucin for binding sites on immobilized native urease. A model polymer that strongly bound urease was used in an in vivo trial using euthymic hairless mice as an infection model.


RESULTS
The blockage of urease-gastric mucin interaction by certain inhibitors revealed an acid-functional lectin-like activity by urease, specifically recognizing bacterial lipopolysaccharides and certain species of polysaccharides, nonbacterial glycolipids, and glycoproteins. Dextran sulfate significantly (P < 0.01) suppressed colonization of mice by H. pylori when given before and/or after challenge.


CONCLUSIONS
The acid-driven high-affinity adherence of H. pylori urease to mucin and lipopolysaccharides contributes to gastric mucosal colonization by the bacterium based on in vivo targeting experiments using specific polysaccharides in a mouse model with acute infection. Acid-functional urease-homing polysaccharides that can interfere with urease-mucin or H. pylori whole cell-mucin interaction in vitro can significantly interfere with colonization by the bacterium in vivo.
Immunology Research Institute, Ghen Corp., Sano, Gifu City, Japan. irig@ghen.co.jp
F C
FC
Icatlo
H
H
Goshima
N
N
Kimura
Y
Y
Kodama
D000143:Acids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D003470:Culture Media / Q000494:pharmacology; D016264:Dextran Sulfate / Q000378:metabolism / Q000494:pharmacology; D005752:Gastric Mucins / Q000378:metabolism / Q000494:pharmacology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D016480:Helicobacter pylori / Q000201:enzymology* / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D011134:Polysaccharides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D013274:Stomach Neoplasms; D013552:Swine; D014407:Tumor Cells, Cultured; D014508:Urea / Q000494:pharmacology; D014510:Urease / Q000378:metabolism*
D000143:Acids; D003470:Culture Media; D005752:Gastric Mucins; D008024:Ligands; D008565:Membrane Proteins; D011134:Polysaccharides; D014508:Urea; D016264:Dextran Sulfate; D014510:Urease