Portal de investigação
Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Marques, MS
- Costa, AC
- Osorio, H
- Pinto, ML
- Relvas, S
- Leite, M
Unidades de investigação
Abstract
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.
Dados da publicação
- ISSN/ISSNe:
- 1949-0984, 1949-0976
- Tipo:
- Article
- Páginas:
- 1-21
- Link para outro recurso:
- www.scopus.com
Gut Microbes Landes Bioscience
Citações Recebidas na Web of Science: 7
Citações Recebidas na Scopus: 15
Documentos
- Não há documentos
Filiações
Keywords
- Helicobacter pylori pathogenesis; bacterial proteases; bacteria-host interactions; junctional adhesion molecule A (JAM-A); F11R; proteomics; PqqE
Financiamento
Proyectos asociados
Unravelling Helicobacter pylori strategies to disrupt cell-cell junctions
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico (Helicobacter) . 2019
Effectiveness of endoscopic resection of colonic lesions > 20mm
Investigador Principal: Mário Jorge Dinis Ribeiro
Estudo Clínico Académico (Colonic lesions) . 2020
Gastric Cancer Morphological, Immunophenotypic and molecular heterogeneity
Investigador Principal: Maria de Fátima Machado Henriques Carneiro
Estudo Clínico Académico . 2020
Citar a publicação
Marques MS,Costa AC,Osorio H,Pinto ML,Relvas S,Dinis M,Carneiro F,Leite M,Figueiredo C. <i>Helicobacter pylori</i> PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity. Gut Microbes. 2021. 13. (1):p. 1-21. IF:9,434. (1).
