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H. pylori infection: Sugar wars

H. pylori colonized on the surface of regenerative epithelium.

Infection of the human stomach by Helicobacter pylori is extremely common, and high-pathogenicity strains are a leading cause of gastric malignancies. Although the factors determining successful colonization are ill-defined, fucosylated antigens are expressed by both invader and host, and are recognized by carbohydrate-binding proteins on the opposing surface.

Certain H. pylori strains were recently shown to induce production of sialyl Lewis X by the gastric epithelia, promoting bacterial adhesion and persistent infection. Induction of host synthesis of a specific fucosylated glycan structure is also a strategy used by a commensal intestinal bacterium, which secretes a fucosidase to harvest L-fucose as an energy source. It was thought that L-fucose might play a similar role in H. pylori interactions with host cells. However, Chun-Hung Lin and colleagues now report in Proceedings of the National Academy of Science of the USA that a different fucose-based relationship occurs between H. pylori and gastric cells. Infection with some H. pylori strains induces secretion of the previously-uncharacterized human fucosidase enzyme FUCA2. Although this secretion probably evolved as a defense strategy to reduce the availability of fucosylated antigens for pathogenic adhesion, H. pylori metabolizes the released sugar and increases Lewis X antigen production, increasing pathogenicity.

Lin and colleagues used a fluorogenic labeling method to metabolically tag fucosylated glycoconjugates in human gastric cell culture. Co-cultured H. pylori was able to take up the labeled fucose both from the host cell surface, and from the cell culture medium. The group used affinity chromatography to isolate the fucosidase activity, and identified the enzyme responsible using mass spectrometry. They were surprised to find that it was not a bacterial enzyme, but human FUCA2. Knockdown of FUCA2 reduced H. pylori attachment in prolonged incubations. CagA is a virulence protein that is translocated from H. pylori to the host, and its detection in host cells indicates successful infection. H. pylori strains isolated from duodenal ulcers and gastric cancer were unable to translocate CagA to FUCA2 knockdown host cells. Furthermore, the expression of FUCA2 by the host cells increased the level of Lewis X antigen in the H. pylori.

The current eradication strategy for H. pylori infections is expensive and complicated. This study suggests that development of an inhibitor of FUCA2 activity might be a promising approach for the prevention of H. pylori-related diseases.

Author: Emma Leah