Glycan dependent Helicobacter spp. and Streptococcus oralis binding to mucins in the gastric and oral mucosal niches

Abstract

Helicobacter pylori infects the stomach of half of the world’s population, while Helicobacter suis colonizes pigs and is the most common non-H. pylori Helicobacter species that also infects human stomach. Infection with Helicobacter spp. is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Streptococcus oralis colonizes human oral cavity and can cause infective endocarditis (IE). First barrier pathogens encounter is the mucus layer constituted by highly glycosylated glycoproteins, the mucins. Mucin glycans provide an extensive surface of interaction for bacteria. Here, we show the interactions of Helicobacter spp. and S. oralis with glycans in the gastric and oral mucosal niche. In paper I, the glycans from H. pylori infected and non-infected human stomachs were characterized by mass spectrometry. An enormous diversity of glycosylation exists in the human stomach. Infection with Helicobacter spp. is associated with large inter- and intra-individual diversity. The differences in glycosylation between mucins from infected and non-infected individuals are reflected by differences in binding of H. pylori to the mucins. In paper II, the binding of different H. pylori strains J99, P12, 26695 and G27 was analyzed. We show that these strains differ in their binding preferences and that mucins from infected or non-infected human stomachs affect the adhesion of different strains differently. Further, we show that infection, rather than inflammation, determines these effects. In paper III, we showed that experimental H. suis infection alters the composition of mucins and their glycosylation in a manner that reduces the amount of H. suis binding glycan structures, decreases H. suis binding ability, and changes mucin phenotype towards more Helicobacter spp. growth promoting. Thus, Helicobacter spp. infections impair the mucus barrier to create a stable niche in the stomach. In paper IV, the carbohydrate binding of IE isolates of S. oralis subspecies was investigated. Mucins were isolated from the saliva from blood group A and B positive individuals. We show that S. oralis adhesion occurs to salivary mucins and the binding differs between strains. S. oralis binding differs between mucins and individuals. Further, we show that S. oralis subsp. oralis binding to oral mucins is mediated by a cell wall anchored surface protein(s) and Leb, SLex and LNT like glycans present on the mucins. We demonstrate that mucin glycans are highly diverse and differ between individuals and with infection status. The glycan repertoire governs the ability of the mucins to bind to pathogens. Helicobacter spp. infection increases the diversity of glycosylation in the host and changes the host mucin composition. Understanding the adhesion mechanisms of H. pylori, H. suis and S. oralis could help develop preventive strategies against these pathogens.