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 Hammarström; Anna Arnqvist; Douglas E. Berg; Serge Muyldermans; Thomas Borén; Han Remaut

doi:10.1016/j.chom.2015.12.004

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

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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.

Original language	English (US)
Pages (from-to)	55-66
Number of pages	12
Journal	Cell Host and Microbe
Volume	19
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2015.12.004
State	Published - 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

Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. / Moonens, Kristof; Gideonsson, Pär; Subedi, Suresh; Bugaytsova, Jeanna; Romaõ, Ema; Mendez, Melissa; Nordén, Jenny; Fallah, Mahsa; Rakhimova, Lena; Shevtsova, Anna; Lahmann, Martina; Castaldo, Gaetano; Brännström, Kristoffer; Coppens, Fanny; Lo, Alvin W.; Ny, Tor; Solnick, Jay V; Vandenbussche, Guy; Oscarson, Stefan; Hammarström, Lennart; Arnqvist, Anna; Berg, Douglas E.; Muyldermans, Serge; Borén, Thomas; Remaut, Han.

In: Cell Host and Microbe, Vol. 19, No. 1, 13.01.2016, p. 55-66.

Research output: Contribution to journal › Article › peer-review

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, AW, Ny, T, Solnick, JV, Vandenbussche, G, Oscarson, S, Hammarström, L, Arnqvist, A, Berg, DE, Muyldermans, S, Borén, T & Remaut, H 2016, 'Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori', Cell Host and Microbe, vol. 19, no. 1, pp. 55-66. https://doi.org/10.1016/j.chom.2015.12.004

Moonens, Kristof ; Gideonsson, Pär ; Subedi, Suresh ; Bugaytsova, Jeanna ; Romaõ, Ema ; Mendez, Melissa ; Nordén, Jenny ; Fallah, Mahsa ; Rakhimova, Lena ; Shevtsova, Anna ; Lahmann, Martina ; Castaldo, Gaetano ; Brännström, Kristoffer ; Coppens, Fanny ; Lo, Alvin W. ; Ny, Tor ; Solnick, Jay V ; Vandenbussche, Guy ; Oscarson, Stefan ; Hammarström, Lennart ; Arnqvist, Anna ; Berg, Douglas E. ; Muyldermans, Serge ; Borén, Thomas ; Remaut, Han. / Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. In: Cell Host and Microbe. 2016 ; Vol. 19, No. 1. pp. 55-66.

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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.",

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