TITLE

A Human Domain Antibody and Lewis Glycoconjugate That Inhibit Binding of Helicobacter pylori to Lewis Receptor and Adhesion to Human Gastric Epithelium

AUTHOR(S)
Younson, Justine; O'Mahony, Rachel; Haiqun Liu; Grant, Steven; Campion, Colin; Jennings, Lisa; Vaira, Dino; Kelly, Charles G.; Roitt, Ivan M.; Holton, John
PUB. DATE
November 2009
SOURCE
Journal of Infectious Diseases;11/15/2009, Vol. 200 Issue 10, p1574
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewisb antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le. The poly-D-lysine-Le hexasaccharide and an Le human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le and sialyl Le or domain antibody 25 and sialyl Le acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Leb glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.
ACCESSION #
45082420

 

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