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A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori

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 cancer...

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Autores principales: Wessler, Silja, Backert, Steffen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772040/
https://www.ncbi.nlm.nih.gov/pubmed/29355242
http://dx.doi.org/10.15698/mic2018.01.611
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author Wessler, Silja
Backert, Steffen
author_facet Wessler, Silja
Backert, Steffen
author_sort Wessler, Silja
collection PubMed
description 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-β(1) 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.
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spelling pubmed-57720402018-01-19 A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori Wessler, Silja Backert, Steffen Microb Cell Microbiology 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-β(1) 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. Shared Science Publishers OG 2017-12-09 /pmc/articles/PMC5772040/ /pubmed/29355242 http://dx.doi.org/10.15698/mic2018.01.611 Text en https://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Microbiology
Wessler, Silja
Backert, Steffen
A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title_full A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title_fullStr A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title_full_unstemmed A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title_short A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
title_sort novel basolateral type iv secretion model for the caga oncoprotein of helicobacter pylori
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772040/
https://www.ncbi.nlm.nih.gov/pubmed/29355242
http://dx.doi.org/10.15698/mic2018.01.611
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