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VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection
Helicobacter pylori (H. pylori) is the causative agent of gastric cancer, making it the only bacterium to be recognized as a Class I carcinogen by the World Health Organization. The virulence factor cytotoxin associated gene A (CagA) is a known oncoprotein that contributes to the development of gast...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328614/ https://www.ncbi.nlm.nih.gov/pubmed/30631092 http://dx.doi.org/10.1038/s41598-018-37095-4 |
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author | Abdullah, Majd Greenfield, Laura K. Bronte-Tinkew, Dana Capurro, Mariana I. Rizzuti, David Jones, Nicola L. |
author_facet | Abdullah, Majd Greenfield, Laura K. Bronte-Tinkew, Dana Capurro, Mariana I. Rizzuti, David Jones, Nicola L. |
author_sort | Abdullah, Majd |
collection | PubMed |
description | Helicobacter pylori (H. pylori) is the causative agent of gastric cancer, making it the only bacterium to be recognized as a Class I carcinogen by the World Health Organization. The virulence factor cytotoxin associated gene A (CagA) is a known oncoprotein that contributes to the development of gastric cancer. The other major virulence factor vacuolating cytotoxin A (VacA), disrupts endolysosomal vesicular trafficking and impairs the autophagy pathway. Studies indicate that there is a functional interplay between these virulence factors by unknown mechanisms. We show that in the absence of VacA, both host-cell autophagy and the proteasome degrade CagA during infection with H. pylori. In the presence of VacA, CagA accumulates in gastric epithelial cells. However, VacA does not affect proteasome function during infection with H. pylori suggesting that VacA−disrupted autophagy is the predominant means by which CagA accumulates. Our studies support a model where in the presence of VacA, CagA accumulates in dysfunctional autophagosomes providing a possible explanation for the functional interplay of VacA and CagA. |
format | Online Article Text |
id | pubmed-6328614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63286142019-01-14 VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection Abdullah, Majd Greenfield, Laura K. Bronte-Tinkew, Dana Capurro, Mariana I. Rizzuti, David Jones, Nicola L. Sci Rep Article Helicobacter pylori (H. pylori) is the causative agent of gastric cancer, making it the only bacterium to be recognized as a Class I carcinogen by the World Health Organization. The virulence factor cytotoxin associated gene A (CagA) is a known oncoprotein that contributes to the development of gastric cancer. The other major virulence factor vacuolating cytotoxin A (VacA), disrupts endolysosomal vesicular trafficking and impairs the autophagy pathway. Studies indicate that there is a functional interplay between these virulence factors by unknown mechanisms. We show that in the absence of VacA, both host-cell autophagy and the proteasome degrade CagA during infection with H. pylori. In the presence of VacA, CagA accumulates in gastric epithelial cells. However, VacA does not affect proteasome function during infection with H. pylori suggesting that VacA−disrupted autophagy is the predominant means by which CagA accumulates. Our studies support a model where in the presence of VacA, CagA accumulates in dysfunctional autophagosomes providing a possible explanation for the functional interplay of VacA and CagA. Nature Publishing Group UK 2019-01-10 /pmc/articles/PMC6328614/ /pubmed/30631092 http://dx.doi.org/10.1038/s41598-018-37095-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Abdullah, Majd Greenfield, Laura K. Bronte-Tinkew, Dana Capurro, Mariana I. Rizzuti, David Jones, Nicola L. VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title | VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title_full | VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title_fullStr | VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title_full_unstemmed | VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title_short | VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection |
title_sort | vaca promotes caga accumulation in gastric epithelial cells during helicobacter pylori infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328614/ https://www.ncbi.nlm.nih.gov/pubmed/30631092 http://dx.doi.org/10.1038/s41598-018-37095-4 |
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