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Helicobacter pylori PqqE is a new virulence factor that cleaves junctional adhesion molecule A and disrupts gastric epithelial integrity.
Marques, Miguel S; Costa, Ana C; Osório, Hugo; Pinto, Marta L; Relvas, Sandra; Dinis-Ribeiro, Mário; Carneiro, Fátima; Leite, Marina; Figueiredo, Ceu.
Afiliação
  • Marques MS; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Costa AC; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Osório H; Faculty of Medicine of the University of Porto, Porto, Portugal.
  • Pinto ML; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Relvas S; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Dinis-Ribeiro M; Faculty of Medicine of the University of Porto, Porto, Portugal.
  • Carneiro F; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Leite M; Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
  • Figueiredo C; Faculty of Medicine of the University of Porto, Porto, Portugal.
Gut Microbes ; 13(1): 1-21, 2021.
Article em En | MEDLINE | ID: mdl-33970782
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Helicobacter pylori / Infecções por Helicobacter / Fatores de Virulência / Molécula A de Adesão Juncional / Mucosa Gástrica Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Gut Microbes Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Portugal

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Helicobacter pylori / Infecções por Helicobacter / Fatores de Virulência / Molécula A de Adesão Juncional / Mucosa Gástrica Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Gut Microbes Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Portugal