Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Kristof Moonens, Pär Gideonsson, Suresh Subedi, Jeanna Bugaytsova, Ema Romaõ, Melissa Mendez, Jenny Nordén, Mahsa Fallah, Lena Rakhimova, Anna Shevtsova, Martina Lahmann, Gaetano Castaldo, Kristoffer Brännström, Fanny Coppens, Alvin W. Lo, Tor Ny, Jay V Solnick, Guy Vandenbussche, Stefan Oscarson, Lennart HammarströmAnna Arnqvist, Douglas E. Berg, Serge Muyldermans, Thomas Borén, Han Remaut

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb 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 Leb 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 Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies.

Original languageEnglish (US)
Pages (from-to)55-66
Number of pages12
JournalCell Host and Microbe
Volume19
Issue number1
DOIs
StatePublished - Jan 13 2016

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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    Moonens, K., Gideonsson, P., Subedi, S., Bugaytsova, J., Romaõ, E., Mendez, M., Nordén, J., Fallah, M., Rakhimova, L., Shevtsova, A., Lahmann, M., Castaldo, G., Brännström, K., Coppens, F., Lo, A. W., Ny, T., Solnick, J. V., Vandenbussche, G., Oscarson, S., ... Remaut, H. (2016). Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host and Microbe, 19(1), 55-66. https://doi.org/10.1016/j.chom.2015.12.004