Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity
Helicobacter pylori infects approximately half of the world’s population and is the strongest risk factor for peptic ulcer disease and gastric cancer, representing a major global health concern. H. pylori persistently colonizes the gastric epithelium, where it subverts the highly organized structure...
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Online Access: | http://dx.doi.org/10.1080/19490976.2021.1921928 |
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doaj-0529de6b4651493e85827130dd2ad71f2021-07-06T12:16:09ZengTaylor & Francis GroupGut Microbes1949-09761949-09842021-01-0113110.1080/19490976.2021.19219281921928Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrityMiguel S. Marques0Ana C. Costa1Hugo Osório2Marta L. Pinto3Sandra Relvas4Mário Dinis-Ribeiro5Fátima Carneiro6Marina Leite7Ceu Figueiredo8i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do PortoCentro Hospitalar Universitário S. JoãoFaculty of Medicine of the University of Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do Portoi3S – Instituto de Investigação e Inovação em Saúde, Universidade do PortoHelicobacter pylori infects approximately half of the world’s population and is the strongest risk factor for peptic ulcer disease and gastric cancer, representing a major global health concern. H. pylori persistently colonizes the gastric epithelium, where it subverts the highly organized structures that maintain epithelial integrity. Here, a unique strategy used by H. pylori to disrupt the gastric epithelial junctional adhesion molecule-A (JAM-A) is disclosed, using various experimental models that include gastric cell lines, primary human gastric cells, and biopsy specimens of infected and non-infected individuals. H. pylori preferentially cleaves the cytoplasmic domain of JAM-A at Alanine 285. Cells stably transfected with full-length JAM-A or JAM-A lacking the cleaved sequence are used in a range of functional assays, which demonstrate that the H. pylori cleaved region is critical to the maintenance of the epithelial barrier and of cell-cell adhesion. Notably, by combining chromatography techniques and mass spectrometry, PqqE (HP1012) is purified and identified as the H. pylori virulence factor that cleaves JAM-A, uncovering a previously unreported function for this bacterial protease. These findings propose a novel mechanism for H. pylori to disrupt epithelial integrity and functions, breaking new ground in the understanding of the pathogenesis of this highly prevalent and clinically relevant infection.http://dx.doi.org/10.1080/19490976.2021.1921928helicobacter pylori pathogenesisbacterial proteasesbacteria-host interactionsjunctional adhesion molecule a (jam-a)/f11rproteomicspqqe |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Miguel S. Marques Ana C. Costa Hugo Osório Marta L. Pinto Sandra Relvas Mário Dinis-Ribeiro Fátima Carneiro Marina Leite Ceu Figueiredo |
spellingShingle |
Miguel S. Marques Ana C. Costa Hugo Osório Marta L. Pinto Sandra Relvas Mário Dinis-Ribeiro Fátima Carneiro Marina Leite Ceu Figueiredo Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity Gut Microbes helicobacter pylori pathogenesis bacterial proteases bacteria-host interactions junctional adhesion molecule a (jam-a)/f11r proteomics pqqe |
author_facet |
Miguel S. Marques Ana C. Costa Hugo Osório Marta L. Pinto Sandra Relvas Mário Dinis-Ribeiro Fátima Carneiro Marina Leite Ceu Figueiredo |
author_sort |
Miguel S. Marques |
title |
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity |
title_short |
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity |
title_full |
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity |
title_fullStr |
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity |
title_full_unstemmed |
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity |
title_sort |
helicobacter pylori pqqe is a new virulence factor that cleaves junctional adhesion molecule a and disrupts gastric epithelial integrity |
publisher |
Taylor & Francis Group |
series |
Gut Microbes |
issn |
1949-0976 1949-0984 |
publishDate |
2021-01-01 |
description |
Helicobacter pylori infects approximately half of the world’s population and is the strongest risk factor for peptic ulcer disease and gastric cancer, representing a major global health concern. H. pylori persistently colonizes the gastric epithelium, where it subverts the highly organized structures that maintain epithelial integrity. Here, a unique strategy used by H. pylori to disrupt the gastric epithelial junctional adhesion molecule-A (JAM-A) is disclosed, using various experimental models that include gastric cell lines, primary human gastric cells, and biopsy specimens of infected and non-infected individuals. H. pylori preferentially cleaves the cytoplasmic domain of JAM-A at Alanine 285. Cells stably transfected with full-length JAM-A or JAM-A lacking the cleaved sequence are used in a range of functional assays, which demonstrate that the H. pylori cleaved region is critical to the maintenance of the epithelial barrier and of cell-cell adhesion. Notably, by combining chromatography techniques and mass spectrometry, PqqE (HP1012) is purified and identified as the H. pylori virulence factor that cleaves JAM-A, uncovering a previously unreported function for this bacterial protease. These findings propose a novel mechanism for H. pylori to disrupt epithelial integrity and functions, breaking new ground in the understanding of the pathogenesis of this highly prevalent and clinically relevant infection. |
topic |
helicobacter pylori pathogenesis bacterial proteases bacteria-host interactions junctional adhesion molecule a (jam-a)/f11r proteomics pqqe |
url |
http://dx.doi.org/10.1080/19490976.2021.1921928 |
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