Helicobacter pylori SabA binding gangliosides of human stomach

Abstract

Adhesion of Helicobacter pylori to the gastric mucosa is a prerequisite for the pathogenesis of H. pylori related diseases. In this study, we investigated the ganglioside composition of human stomach as the target for attachment mediated by H. pylori SabA (sialic acid binding adhesin). Acid glycosphingolipids were isolated from human stomach and separated into subfractions, which were characterized by mass spectrometry and by binding of antibodies, bacteria, and Solanum tuberosum lectin. H. pylori SabA binding gangliosides were characterized as Neu5Acα3-neolactohexaosylceramide and Neu5Acα3-neolactooctaosylceramide, while the other acid human stomach glycosphingolipids characterized (sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acα3-neolactotetraosylceramide, GD1a and GD1b) were not recognized by the bacteria. Defining H. pylori binding glycosphingolipids of the human gastric mucosa will be useful to specifically target this microbe-host interaction for therapeutic intervention.

Helicobacter pylori–binding nonacid glycosphingolipids in the human stomach

“…However, in individuals with little or no Le b on the gastric epithelium, an enhanced H. pylori colonization density is obtained by interactions between the SabA adhesin and sialylated gastric glycoconjugates (40). In a recent study, we have characterized the acid glycosphingolipids of the human stomach (19) and identified two minor H. pylori SabA-binding gangliosides as Neu5Ac␣3-neolactohexaosylceramide (Neu5Ac␣3Gal␤4GlcNAc␤3Gal␤4-GlcNAc␤3Gal␤4Glc␤1Cer) and Neu5Ac␣3-neolactooctaosylceramide (Neu5Ac␣3Gal␤4GlcNAc␤3Gal␤4GlcNAc␤3Gal␤4 GlcNAc␤3Gal␤4Glc␤1Cer), which thus might function as adhesion factors for SabA-expressing H. pylori.…”

“…A few reports with characterization of selected human gastric glycosphingolipids are available (17,18), but a thorough characterization with the methods available today has not been done. In a recent study, we have characterized the acid glycosphingolipids of human stomach (19) and identified two minor H. pylori SabA-binding gangliosides as Neu5Ac␣3-neolactohexaosylceramide (Neu5Ac␣3Gal␤4GlcNAc␤3Gal␤4GlcNAc␤3Gal␤4 Glc␤1Cer) and Neu5Ac␣3-neolactooctaosylceramide (Neu5Ac␣3 Gal␤4GlcNAc␤3Gal␤4GlcNAc␤3Gal␤4GlcNAc␤3Gal␤4Glc ␤1Cer), whereas the other acid human stomach glycosphingolipids characterized (sulfatide and the gangliosides GM3, GD3, GM1, Neu5Ac␣3-neolactotetraosylceramide, GD1a, and GD1b) were not recognized by the bacteria. The aim of the present study was to characterize the nonacid glycosphingolipids of the human stomach, with particular interest in components with H. pylori-binding activity.…”

Characterization of glycosphingolipids from gastrointestinal stromal tumours

“…*marks a non-oligosaccharide contaminant. www.nature.com/scientificreports/ Overall the glycosphingolipid patterns of the three gastric GISTs had a high similarity with the glycosphingolipids of the human stomach 18,27 . The non-acid glycosphingolipids of human stomach had a high degree of structural complexity, and the composition of glycosphingolipids differed for individuals of separate blood groups.…”

“…The A(Rh +)P, and A(Rh +)p stomachs had lactotetraosylceramide, the x 2 and the H type 1 pentaosylceramides, neolactohexaosylceramide the Le b hexaosylceramide and the A type 1/ALe b heptaosylceramide 18 . The acid human stomach glycosphingolipids characterized were sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acα3-neolactotetraosylceramide, Neu5Acα3-neolactohexaosylceramide and Neu5Acα3-neolactooctaosylceramide, GD1a and GD1b 27 . The major difference observed was the relatively low levels of sulfatide in the GIST tumours compared to the human stomach 27 .…”

“…The acid human stomach glycosphingolipids characterized were sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acα3-neolactotetraosylceramide, Neu5Acα3-neolactohexaosylceramide and Neu5Acα3-neolactooctaosylceramide, GD1a and GD1b 27 . The major difference observed was the relatively low levels of sulfatide in the GIST tumours compared to the human stomach 27 .…”