Regulation of Helicobacter pylori by O-glycan

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Aim of this study is to determine the role of O-glycans expressed in the gastric mucosa infected by Helicobacter pylori (H. pylori). The gland mucin secreted from lower portion of the gastric mucosa contains α1,4-GlcNAc-capped O-glycan (αGlcNAc). H.pylori exclusively colonizes the surface mucin, whereas this microbe is not found in the gland mucin. We demonstrated that H.pylori cultured in the presence of αGlcNAc exhibited its reduced cell growth and motility as well as abnormal morphology and that cholesteryl-α-D-glucopyranoside (CGL), a major cell wall of H.pylori, was critical for their survival. We identified CHLαGcT gene, which encodes the glycosyltransferase responsible for the biosynthesis of CGL, by expression cloning, and showed that its enzymatic activity was inhibited by αGlcNAc. These results combined together indicate that αGlcNAc functions as a natural antibiotic against H.pylori infection by suppressing the CGL biosynthesis. By manipulating the gene encoding α1,4-N-acety … More lglucosaminyltransferase responsible for αGlcNAc biosynthesis, we have generated both knockout mice deficient in αGlcNAc and transgenic mice ectopically expressing αGlcNAc in the surface mucin. The future study will be directed to elucidate the in vivo function of αGlcNAc in the gastric mucosa using these genetically-engineered mice.We then investigated the mechanism for lymphocyte infiltration in chronic active gastritis caused by H.pylori infection. It was demonstrated that the number of high endothelial venule (HEV)-like vessels expressing O-glycan having 6-sulfo sialyl Lewis X (ssLeX) increased as chronic inflammation progressed. We also found that these HEV-like vessels were bound by L-selectin-IgM chemeric protein. These results indicated that the L-selectin-mediated lymphocyte homing takes place in the chronic active gastritis.Thus, it is concluded that the two types of O-glycans, αGlcNAc and ssLeX, play pivotal roles in the gastric mucosa infected by H.pylori in a carbohydrate-dependent manner. Less