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

Younson, Justine; O'Mahony, Rachel; Haiqun Liu; Grant, Steven; Campion, Colin; Jennings, Lisa; Vaira, Dino; Kelly, Charles G.; Roitt, Ivan M.; Holton, John
November 2009
Journal of Infectious Diseases;11/15/2009, Vol. 200 Issue 10, p1574
Academic Journal
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.


Related Articles

  • Helicobacter pyloriIncreases the Epithelial Permeability to a Food Antigen in Human Gastric Biopsies. Matysiak-Budnik, Tamara; Coffin, Benoît; Lavergne-Slove, Anne; Sabate, Jean-Marc; Mégraud, Francis; Heyman, Martine // American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p225 

    AIM: We have previously shown thatH. pyloriincreases the passage of intact protein across the digestive epithelium,in vitroandin vivoin mice. The aim of this study was to test whetherH. pylorican alter gastric permeability to a food-type antigen in humans.METHODS: Antral and corpus gastric...

  • Role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use in bleeding peptic ulcers in Japan. Ootani, Hibiki; Iwakiri, Ryuichi; Shimoda, Ryo; Nakahara, Shin; Amemori, Sadahiro; Fujise, Takehiro; Kikkawa, Atsushi; Tsunada, Seiji; Sakata, Hiroyuki; Fujimoto, Kazuma // Journal of Gastroenterology;Jan2006, Vol. 41 Issue 1, p41 

    Background. Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known major causes of peptic ulcers. This study aimed to characterize the features of bleeding peptic ulcers in Japan. Methods. This prospective study evaluated 116 patients revealed to have...

  • Confirmation of Successful Therapy of Helicobacter pylori Infection: Number and Site of Biopsies or a Rapid Urease Test. El-Zimaity, Hala M. T.; Al-Assi, Mohammad T.; Genta, Robert M.; Graham, David Y. // American Journal of Gastroenterology;Nov1995, Vol. 90 Issue 11, p1962 

    Background: Although a number of tests have been described to detect the presence of Helicobacter pylori in biopsy specimens, studies of positive and negative value have largely been performed on untreated patients; testing the reliability of posttherapy has not been done. Methods: We...

  • Infectious disease associations in advanced stage, indolent lymphoma (follicular and nonfollicular): developing a lymphoma prevention strategy. C. S. Portlock; P. Hamlin; A. Noy; W. Chey; C. A. Gaydos; L. Palomba; I. Schwartz; S. Corcoran; L. Rosenzweig; D. Walker; G. Papanicolaou; A. Markowitz // Annals of Oncology;Feb2008, Vol. 19 Issue 2, p254 

    Background: Eradication of Helicobacter pylori in gastric mucosa-associated lymphoid tumor can result in lymphoma remission. We prospectively identified/treated infections in nonbulky, advanced stage indolent lymphoma (follicular; nonfollicular lymphoma) eligible for observation. Materials and...

  • Facing resistance of H.pylori infection. Zali, Mohammad Reza // Gastroenterology & Hepatology from Bed to Bench;Jan2011, Vol. 4 Issue 1, p3 

    Helicobacter pylori is an important human pathogen and a gram-negative, spiral shaped and microaerophilic bacteria with persistence colonization in gastric mucosa, causes gastroduodenal inflammation and destruction, resulting in diseases such as duodenal ulcer disease, gastric ulcer disease....

  • Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions. Yu, J.; Leung, W.K.; Go, M.Y.Y.; Chan, M.C.W.; To, K.F.; Ng, E.K.W.; Chan, F.K.L.; Ling, T.K.W.; Chung, S.C.S.; Sung, J.J.Y. // Gut;Oct2002, Vol. 51 Issue 4, p480 

    Background: Helicobacter pylori blood group antigen binding adhesin (BabA) mediates bacterial adherence to human blood group antigens on gastric epithelium. Although strains harbouring babA2 were recently found to be associated with peptic ulcer and gastric cancer, the role of babA2 in cellular...

  • The Interaction of Helicobacter pylori with the Adherent Mucus Gel Layer Secreted by Polarized HT29-MTX-E12 Cells. Dolan, Brendan; Naughton, Julie; Tegtmeyer, Nicole; May, Felicity E. B.; Clyne, Marguerite // PLoS ONE;Oct2012, Vol. 7 Issue 10, Special section p1 

    Helicobacter pylori colonises the gastric mucosa of humans. The majority of organisms live in mucus. These organisms are an important reservoir for infection of the underlying epithelium. Cell culture models for H. pylori infection do not normally possess a mucus layer. The interaction of H....

  • Why are the results inconsistent on relationships between Se and Le genotypes and continuous infection of H. pylori? Kikuchi, Shogo // Journal of Gastroenterology;2004, Vol. 39 Issue 8, p807 

    Helicobacter pylori attaches specific surface carbohydrate structures of gastric mucosa such as Lewis b and H type I antigens. It is well known that age and stomach disease of the subjects, such as peptic ulcer and gastritis, are closely related to prevalence of H. pylori. The studies evaluated...

  • Relation of systemic IgG1 and IgG2 immune response to Helicobacter pylori specifici antibodies in children. Bode, G.; Zöllner, I.; Brenner, H.; Rothenbacher, D. // Gut;Sep2002 Supplement 2, Vol. 51, pA33 

    Objective An optimal host response against H. pylori in the gastric mucosa demands for highly specialized reactions which are primarily controlled by CD4[sup +] T helper (Th1/Th2) cells. An indirect characterization of the Th1/Th2 immune response by measuring systemic titres of IgG subclasses...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics