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H. pylori bacteria manipulate host glycosylation patterns to aid their own colonization Helicobacter pylori are spiral-shaped bacteria unique in their ability to survive in the harsh stomach environment. Although most people who carry H. pylori never experience any symptoms, in some cases chronic inflammation caused by the infection can lead to certain kinds of ulcers, or even cancer. In the June 2008 issue of the Journal of Clinical Investigation, researchers at the University of Porto in Portugal and the Consortium for Functional Glycomics (CFG) now show that interaction with this bacterium induces changes in the expression of cell surface antigens in the stomach in a way that helps H. pylori grab hold and initiate colonization, the first steps in establishing infection. H. pylori adherence to host cells is mediated by proteins on their surface that bind carbohydrate ligands on the epithelial cells lining the stomach. H. pylori strains containing a chunk of genes called the cag pathogenicity island (cagPAI+ strains) are more virulent than strains lacking this pathogenicity island (cagPAI-), and they are better able to adhere to and colonize host cells. CagPAI+ strains of H. pylori are also associated with a higher incidence of gastric disease. In this study, resources available from the CFG's Gene Microarray Core were used to examine how H. pylori infection affects the expression of host receptors. The authors used a gene microarray that probes for the expression of 1,031 human genes encoding carbohydrate biosynthesis enzymes, sugar transporters, and glycan-binding proteins, and many other carbohydrate-related, or "glyco", genes. The results revealed altered expression of four times as many glycogenes in gastric cells infected with cagPAI+ H. pylori strains than in cells exposed to the less virulent cagPAI- H. pylori. One key glycogene upregulated in response to cagPAI+ H. pyloriinfection was b3GnT5, which encodes a transferase enzyme that links N-acetylglucosamine (GlcNAc) sugars to glycoproteins and lipids. b3GnT5 is necessary for the proper assembly of carbohydrates decorating a particular glycolipid known as the sialyl-Lewis x blood group antigen. Sialyl-Lewis x is also one of the carbohydrate ligands, or host receptors, employed by H. pylori for adherence to host cells, suggesting that these bacteria manipulate host gene expression for their own benefit. Indeed, when the authors of this study overexpressed b3GnT5 in gastric cells, they noticed a subsequent increase in expression of sialyl-Lewis x, which in turn enhanced the ability of H. pylori to adhere to the cells. This study, combined with others that show changes in H. pylori gene expression upon interaction with gastric cells, clearly demonstrates that the balance between healthy and disease states relies on a complex interplay between host and pathogen, even at the genetic level. Heather Buschman
Original Paper: Marcos NT, Magalh‹es A, Ferreira B, Oliveira MJ, Carvalho AS, Mendes N, Gilmartin T, Head SR, Figueiredo C, David L, Santos-Silva F, Reis CA. Helicobacter pylori induces b3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x. J Clin Invest. 2008 Jun;118(6):2325-36. |