title: Helicobacter pylori induces beta3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl-Lewis x.
abstract: Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid-binding adhesin (SabA), which binds the carbohydrate structure sialyl-Lewis x. Sialyl-Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-related gene expression profile of a human gastric carcinoma cell line following H. pylori infection. We observed that H. pylori significantly altered expression of 168 of the 1,031 human genes tested by microarray, and the extent of these alterations was associated with the pathogenicity of the H. pylori strain. A highly pathogenic strain altered expression of several genes involved in glycan biosynthesis, in particular that encoding beta3 GlcNAc T5 (beta3GnT5), a GlcNAc transferase essential for the biosynthesis of Lewis antigens. beta3GnT5 induction was specific to infection with highly pathogenic strains of H. pylori carrying a cluster of genes known as the cag pathogenicity island, and was dependent on CagA and CagE. Further, beta3GnT5 overexpression in human gastric carcinoma cell lines led to increased sialyl-Lewis x expression and H. pylori adhesion. This study identifies what we believe to be a novel mechanism by which H. pylori modulates the biosynthesis of the SabA ligand in gastric cells, thereby strengthening the epithelial attachment necessary to achieve successful colonization.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Nuno T
authors.initials: NT
authors.lastname: Marcos
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.forename: Bibiana
authors.initials: B
authors.lastname: Ferreira
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Oliveira
authors.forename: Ana S
authors.initials: AS
authors.lastname: Carvalho
authors.forename: Nuno
authors.initials: N
authors.lastname: Mendes
authors.forename: Tim
authors.initials: T
authors.lastname: Gilmartin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Head
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.forename: Filipe
authors.initials: F
authors.lastname: Santos-Silva
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D010802:Phylogeny; D000080506:Sialyl Lewis X Antigen; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology*; D014162:Transfection
chemical_list: D018829:Adhesins, Bacterial; D008024:Ligands; D009844:Oligosaccharides; C500808:SabA protein, Helicobacter pylori; D000080506:Sialyl Lewis X Antigen; D017351:N-Acetylglucosaminyltransferases; C067641:lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase