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Science 25 February 2000:
Vol. 287. no. 5457, pp. 1497 - 1500
DOI: 10.1126/science.287.5457.1497
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Reports

Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

Stefan Odenbreit, Jürgen Püls, Bettina Sedlmaier, Elke Gerland, Wolfgang Fischer, Rainer Haas *

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.

Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany.
*   To whom correspondence should be addressed at Max von Pettenkofer Institute, Pettenkoferstrasse 9a, D-80336 Munich, Germany. E-mail: haas{at}m3401.mpk.med.uni-muenchen.de

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J R Bebb, D P Letley, R J Thomas, F Aviles, H M Collins, S A Watson, N M Hand, A Zaitoun, and J C Atherton (2003)
Gut 52, 1408-1413
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Cytoskeletal rearrangements in gastric epithelial cells in response to Helicobacter pylori infection.
B. Su, P. J.M. Ceponis, and P. M. Sherman (2003)
J. Med. Microbiol. 52, 861-867
   Abstract »    Full Text »    PDF »
Complete genome sequence and analysis of Wolinella succinogenes.
C. Baar, M. Eppinger, G. Raddatz, J. Simon, C. Lanz, O. Klimmek, R. Nandakumar, R. Gross, A. Rosinus, H. Keller, et al. (2003)
PNAS 100, 11690-11695
   Abstract »    Full Text »    PDF »
Interleukin 1{beta} induces gastric epithelial cell matrix metalloproteinase secretion and activation during Helicobacter pylori infection.
M Gooz, M Shaker, P Gooz, and A J Smolka (2003)
Gut 52, 1250-1256
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Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation.
B. Gebert, W. Fischer, E. Weiss, R. Hoffmann, and R. Haas (2003)
Science 301, 1099-1102
   Abstract »    Full Text »    PDF »
Helicobacter pylori Induces RANTES through Activation of NF-{kappa}B.
N. Mori, A. M. Krensky, R. Geleziunas, A. Wada, T. Hirayama, C. Sasakawa, and N. Yamamoto (2003)
Infect. Immun. 71, 3748-3756
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Identification of cagA Tyrosine Phosphorylation DNA Motifs in Helicobacter pylori Isolates from Peptic Ulcer Patients by Novel PCR-Restriction Fragment Length Polymorphism and Real-Time Fluorescence PCR Assays.
R. J. Owen, S. I. Sharp, S. A. Chisholm, and S. Rijpkema (2003)
J. Clin. Microbiol. 41, 3112-3118
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Effects of Helicobacter pylori on intracellular Ca2+ signaling in normal human gastric mucous epithelial cells.
K. L. Marlink, K. D. Bacon, B. C. Sheppard, H. Ashktorab, D. T. Smoot, T. L. Cover, C. W. Deveney, and M. J. Rutten (2003)
Am J Physiol Gastrointest Liver Physiol 285, G163-G176
   Abstract »    Full Text »    PDF »
Helicobacter pylori Infection Induces Interleukin-8 Receptor Expression in the Human Gastric Epithelium.
F. Backhed, E. Torstensson, D. Seguin, A. Richter-Dahlfors, and B. Rokbi (2003)
Infect. Immun. 71, 3357-3360
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Disruption of the Epithelial Apical-Junctional Complex by Helicobacter pylori CagA.
M. R. Amieva, R. Vogelmann, A. Covacci, L. S. Tompkins, W. J. Nelson, and S. Falkow (2003)
Science 300, 1430-1434
   Abstract »    Full Text »    PDF »
Distinctive Patterns of Gene Expression in Premalignant Gastric Mucosa and Gastric Cancer.
A. Boussioutas, H. Li, J. Liu, P. Waring, S. Lade, A. J. Holloway, D. Taupin, K. Gorringe, I. Haviv, P. V. Desmond, et al. (2003)
Cancer Res. 63, 2569-2577
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Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response.
Y. Churin, L. Al-Ghoul, O. Kepp, T. F. Meyer, W. Birchmeier, and M. Naumann (2003)
J. Cell Biol. 161, 249-255
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Heterogeneity of cag Genotypes in Helicobacterpylori Isolates from Human Biopsy Specimens.
M. L. Tomasini, S. Zanussi, M. Sozzi, R. Tedeschi, G. Basaglia, and P. De Paoli (2003)
J. Clin. Microbiol. 41, 976-980
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Production of the Type IV Secretion System Differs among Brucella Species as Revealed with VirB5- and VirB8-Specific Antisera.
B. Rouot, M.-T. Alvarez-Martinez, C. Marius, P. Menanteau, L. Guilloteau, R.-A. Boigegrain, R. Zumbihl, D. O'Callaghan, N. Domke, and C. Baron (2003)
Infect. Immun. 71, 1075-1082
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Colonization of C57BL/6J and BALB/c Wild-Type and Knockout Mice with Helicobacter pylori: Effect of Vaccination and Implications for Innate and Acquired Immunity.
K. Panthel, G. Faller, and R. Haas (2003)
Infect. Immun. 71, 794-800
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Helicobacter pylori genotyping in gastric adenocarcinoma and MALT lymphoma by multiplex PCR analyses of paraffin wax embedded tissues.
C I Koehler, M B Mues, H P Dienes, J Kriegsmann, P Schirmacher, and M Odenthal (2003)
Mol. Pathol. 56, 36-42
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repp86: A Human Protein Associated in the Progression of Mitosis.
H.-J. Heidebrecht, S. Adam-Klages, M. Szczepanowski, M. Pollmann, F. Buck, E. Endl, M.-L. Kruse, P. Rudolph, and R. Parwaresch (2003)
Mol. Cancer Res. 1, 271-279
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Attenuation of Helicobacter pylori CagA{middle dot}SHP-2 Signaling by Interaction between CagA and C-terminal Src Kinase.
R. Tsutsumi, H. Higashi, M. Higuchi, M. Okada, and M. Hatakeyama (2003)
J. Biol. Chem. 278, 3664-3670
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