Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion.
The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA(+)) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.
Odenbreit
S
S
Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany.
Püls
J
J
Sedlmaier
B
B
Gerland
E
E
Fischer
W
W
Haas
R
R
D020816:Amino Acid Motifs; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology*; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D019833:Genistein / Q000494:pharmacology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C080866:cagA protein, Helicobacter pylori; D019000:Phosphotyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine