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Science 30 May 2003:
Vol. 300. no. 5624, pp. 1430 - 1434
DOI: 10.1126/science.1081919
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Reports

Disruption of the Epithelial Apical-Junctional Complex by Helicobacter pylori CagA

Manuel R. Amieva,1,2*{dagger} Roger Vogelmann,3* Antonello Covacci,5 Lucy S. Tompkins,1,4 W. James Nelson,3 Stanley Falkow1,4

Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ectopic assembly of tight-junction components at sites of bacterial attachment, and altering the composition and function of the apical-junctional complex. Long-term CagA delivery to polarized epithelia caused a disruption of the epithelial barrier function and dysplastic alterations in epithelial cell morphology. CagA appears to target H. pylori to host cell intercellular junctions and to disrupt junction-mediated functions.

1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
3 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4 Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
5 Istituto Ricerche Immunobiologiche Siena–Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: amieva{at}stanford.edu

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