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 Lewisb and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewisb oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Leb. The poly-D-lysine-Leb hexasaccharide and an Leb 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 Leb and sialyl Lex or domain antibody 25 and sialyl Lex 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
Younson J, O’Mahony R, Liu H, Grant S, Campion C, Vaira D, et al. (2009). A human domain antibody and Lewisb–glyconjugate that inhibit binding of Helicobacter pylori to Lewisb receptor and inhibit bacterial adhesion to human gastric epithelium. THE JOURNAL OF INFECTIOUS DISEASES, 200, 1574-1582 [10.1086/644596].
A human domain antibody and Lewisb–glyconjugate that inhibit binding of Helicobacter pylori to Lewisb receptor and inhibit bacterial adhesion to human gastric epithelium
VAIRA, BERARDINO;
2009
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 Lewisb and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewisb oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Leb. The poly-D-lysine-Leb hexasaccharide and an Leb 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 Leb and sialyl Lex or domain antibody 25 and sialyl Lex 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 infectionI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
