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Structural Insights into Polymorphic ABO Glycan Binding by
Helicobacter pylori.
Moonens K1, Gideonsson P2, Subedi S1, Bugaytsova J2, Romaõ E3, Mendez M2, Nordén J2, Fallah
M2, Rakhimova L2, Shevtsova A2, Lahmann M4, Castaldo G1, Brännström K2, Coppens F1, Lo AW1, Ny T2, Solnick
JV5, Vandenbussche G6, Oscarson S7, Hammarström L8, Arnqvist A2, Berg DE9, Muyldermans S3, Borén
T10, Remaut H11.
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 redoxactive pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected
Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.
Copyright © 2016 Elsevier Inc. All rights reserved.
Cell Host Microbe. 2016 Jan 13;19(1):55-66. doi: 10.1016/j.chom.2015.12.004.