Virulent Shigella flexneri Affects Secretion, Expression, and Glycosylation of Gel-Forming Mucins in Mucus-Producing Cells
| Autor: | Philippe J. Sansonetti, Yannick Rossez, Natalie Fischer, Catherine Robbe Masselot, Pascal Roux, Marie Joncquel Chevalier-Curt, Brice Sperandio |
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| Přispěvatelé: | Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imagerie Dynamique (Plate-Forme) (PFID), Institut Pasteur [Paris] (IP), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), The research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreement EIMID ITN no. 264388. P. J. Sansonetti is supported by the European Research Council (HOMEOEPITH project) and by the Howard Hughes Medical Institute., European Project: 264388,EC:FP7:PEOPLE,FP7-PEOPLE-2010-ITN,EIMID ITN(2010), European Project: 232798,EC:FP7:ERC,ERC-2008-AdG,HOMEOEPITH(2009), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses, Université de Lille, LillOA, European Initiative for basic research in Microbiology and Infectious Diseases - EIMID ITN - - EC:FP7:PEOPLE2010-10-01 - 2014-09-30 - 264388 - VALID, Homeostasis and rupture of the gut epithelium in the presence of commensals and pathogens - HOMEOEPITH - - EC:FP7:ERC2009-02-01 - 2013-07-31 - 232798 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Glycosylation
MESH: Shigella flexneri MESH: Gels MESH: HT29 Cells Immunology MESH: Virulence MESH: Mucins Biology MESH: Trefoil Factor-2 Microbiology Shigella flexneri 03 medical and health sciences chemistry.chemical_compound Electrolytes MESH: Electrolytes MESH: Endoplasmic Reticulum Stress Humans Secretion education 030304 developmental biology chemistry.chemical_classification 0303 health sciences education.field_of_study MESH: Humans Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Virulence MESH: Peptides 030302 biochemistry & molecular biology Mucin Trefoil factor 2 Mucins biology.organism_classification Endoplasmic Reticulum Stress MESH: Gene Expression Regulation Intestinal epithelium Mucus [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry Infectious Diseases chemistry Gene Expression Regulation Parasitology Trefoil Factor-2 Glycoprotein Peptides Gels HT29 Cells |
| Zdroj: | Infection and Immunity Infection and Immunity, 2013, Infection and immunity, 81 (10), pp.3632-3643. ⟨10.1128/IAI.00551-13⟩ Infection and Immunity, American Society for Microbiology, 2013, Infection and immunity, 81 (10), pp.3632-3643. ⟨10.1128/IAI.00551-13⟩ |
| ISSN: | 0019-9567 1098-5522 |
| DOI: | 10.1128/IAI.00551-13 |
| Popis: | Mucin glycoproteins are secreted in large amounts by the intestinal epithelium and constitute an efficient component of innate immune defenses to promote homeostasis and protect against enteric pathogens. In this study, our objective was to investigate how the bacterial enteropathogen Shigella flexneri , which causes bacillary dysentery, copes with the mucin defense barrier. We report that upon in vitro infection of mucin-producing polarized human intestinal epithelial cells, virulent S. flexneri manipulates the secretion of gel-forming mucins. This phenomenon, which is triggered only by virulent strains, results in accumulation of mucins at the cell apical surface, leading to the appearance of a gel-like structure that favors access of bacteria to the cell surface and the subsequent invasion process. We identify MUC5AC, a gel-forming mucin, as a component of this structure. Formation of this gel does not depend on modifications of electrolyte concentrations, induction of trefoil factor expression, endoplasmic reticulum stress, or response to unfolded proteins. In addition, transcriptional and biochemical analyses of infected cells reveal modulations of mucin gene expression and modifications of mucin glycosylation patterns, both of which are induced by virulent bacteria in a type III secretion system-dependent manner. Thus, S. flexneri has developed a dedicated strategy to alter the mucus barrier by targeting key elements of the gel-forming capacity of mucins: gene transcription, protein glycosylation, and secretion. |
| Databáze: | OpenAIRE |
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