Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.

TitleStructural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.
Publication TypeJournal Article
Year of Publication2016
AuthorsMoonens, K., P. Gideonsson, S. Subedi, J. Bugaytsova, E. Romão, M. Mendez, J. Nordén, M. Fallah, L. Rakhimova, A. Shevtsova, M. Lahmann, G. Castaldo, K. Brännström, F. Coppens, A. W. Lo, T. Ny, J. V. Solnick, G. Vandenbussche, S. Oscarson, L. Hammarström, A. Arnqvist, D. E. Berg, S. Muyldermans, T. Borén, and H. Remaut
JournalCell Host Microbe
Volume19
Issue1
Pagination55-66
Date Published2016 Jan 13
ISSN1934-6069
KeywordsABO Blood-Group System, Adhesins, Bacterial, Animals, Binding Sites, Helicobacter Infections, Helicobacter pylori, Humans, Mice, Models, Molecular, Polysaccharides, Protein Binding
Abstract

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

DOI10.1016/j.chom.2015.12.004
Alternate JournalCell Host Microbe
PubMed ID26764597
PubMed Central IDPMC4793151
Grant ListR01 AI070803 / AI / NIAID NIH HHS / United States
R01 AI081037 / AI / NIAID NIH HHS / United States
subject_category: 
Research group: