A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
Authors:Silja Wessler1 and Steffen Backert2
doi: 10.15698/mic2018.01.611
Volume 5, pp. 60 to 62, published 09/12/2017.
1 Dept. of Molecular Biology, University of Salzburg, Austria.
2 Dept. of Biology, Division of Microbiology, University of Erlangen-Nuremberg, Germany.
Keywords:
E-cadherin, focal adhesions, Helicobacter, protease, HtrA, CagA, T4SS, claudin, occludin, integrin
Corresponding Author(s):
Conflict of interest statement:
The authors state that they have no conflict of interests.
Please cite this article as:
Silja Wessler and Steffen Backert (2017). A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori. Microbial Cell 5(1): 60-62. doi: 10.15698/mic2018.01.611
© 2017 Wessler and Backert. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Intercellular junctions are crucial structural elements for the formation and maintenance of epithelial barrier functions to control homeostasis or protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of numerous cancers as well as multiple infectious diseases. Many bacterial pathogens harbor type IV secretion systems (T4SSs), which translocate virulence factors into host cells to hijack cellular processes. The pathology of the gastric pathogen and type-I carcinogen Helicobacter pylori strongly depends on a T4SS encoded by the cag pathogenicity island (cagPAI). This T4SS forms a needle-like pilus and its activity is accomplished by the pilus-associated factors CagL, CagI and CagY which target the host integrin-β1 receptor followed by injection of the CagA oncoprotein into non-polarized AGS gastric epithelial cells. The finding of a T4SS receptor, however, suggested the presence of a sophisticated control mechanism for the injection of CagA. In fact, integrins constitute a group of basolateral receptors, which are normally absent at apical surfaces of the polarized epithelium in vivo. Our new results demonstrate that T4SS-pilus formation during H. pylori infection of polarized epithelial cells occurs preferentially at basolateral sites, and not at apical membranes (Tegtmeyer et al., 2017). We propose a stepwise process how H. pylori interacts with components of intercellular tight junctions (TJs) and adherens junctions (AJs), followed by contacting integrin-based focal adhesions to disrupt and transform the epithelial cell layer in the human stomach. The possible impact of this novel signaling cascade on pathogenesis during infection is reviewed.