Disruption of the epithelial apical-juncitonal complex by

Helicobacter pylori CagA

Speaker: 林貞杏

Time: pm 2:00~3:00 10/29/2003

Room: 601

Commentator: 許博翔醫師

Abstract:

Helicobacter pylori, a gram-negative spiral-bacillus, colonizes the gastric mucosa of human, and is related with the cause of chronic active gastritis and peptic ulcer. Many important determinants of H. pylori stomach colonization and pathogenicity, such as the urease, vacuolating cytotoxin A (VacA), and cytotoxin-associated gene A (CagA), have been described. CagA, the product of the cagA gene, is carried in the virulent type I strains of H. pylori, and is injected into the host epithelial cells by using a type IV secretion system. However, the significance of the CagA localization in the host epithelial cells remains unclear. In this study, the authors examined the consequences of the attachment of H. pylori to, and translocation of CagA into, the polarized Madin-Darby canine kidney (MDCK) cells. They found that H. pylori preferentially attached near cell-cell junction and altered the localization of tight-junction scaffolding protein ZO-1, and these properties are CagA-dependent. Furthermore, interaction of H. pylori with MDCK cells resulted in leakage of ruthenium red into the basal-lateral space, indicating disruption of the barrier function of the apical-junctional complex. In addition, long-term treatment of MDCK cells with H. pylori caused morphological alterations of the cells. When they examined the fractionated membranes of the infected MDCK cells, they found that the distributions of ZO-1 and the transmembrane protein junctional adhesion molecule, JAM, shifted from discrete fractions to that containing CagA. This demonstrates that the structure of the apical-junctional complex has changed probably via recruitment of these proteins by CagA. Based on these findings, the authors concluded that CagA mediates targeting of H. pylori to host cell intercellular junctions and disruption of the apical-junctional complex function.

References:

1.          Amieva, M. R., Vogelmann, R., Comacci, A., Tompkins, L. S., Nelson, W. J., and Falkow, S. 2003 Disruption of the epithelial apical-juncitonal complex by Helicobacter pylori CagA. Science300:1430-1434

2.          Odenbreit, S., Puls, J., Sedlmaier, B., Gerland, E., Fischer, W., and Hass. R. 2000 Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:14971500