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https://hdl.handle.net/10216/119046
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DC Field | Value | Language |
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dc.creator | Magalhães, A | |
dc.creator | Rossez, Y | |
dc.creator | Robbe-Masselot, C | |
dc.creator | Maes, E | |
dc.creator | Gomes, J | |
dc.creator | Shevtsova, A | |
dc.creator | Bugaytsova, J | |
dc.creator | Borén, T | |
dc.creator | Reis, CA | |
dc.date.accessioned | 2019-02-21T12:16:24Z | - |
dc.date.available | 2019-02-21T12:16:24Z | - |
dc.date.issued | 2016 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://hdl.handle.net/10216/119046 | - |
dc.description.abstract | The gastrointestinal tract is lined by a thick and complex layer of mucus that protects the mucosal epithelium from biochemical and mechanical aggressions. This mucus barrier confers protection against pathogens but also serves as a binding site that supports a sheltered niche of microbial adherence. The carcinogenic bacteria Helicobacter pylori colonize the stomach through binding to host glycans present in the glycocalyx of epithelial cells and extracellular mucus. The secreted MUC5AC mucin is the main component of the gastric mucus layer, and BabA-mediated binding of H. pylori to MUC5AC confers increased risk for overt disease. In this study we unraveled the O-glycosylation profile of Muc5ac from glycoengineered mice models lacking the FUT2 enzyme and therefore mimicking a non-secretor human phenotype. Our results demonstrated that the FUT2 determines the O-glycosylation pattern of Muc5ac, with Fut2 knock-out leading to a marked decrease in a1,2-fucosylated structures and increased expression of the terminal type 1 glycan structure Lewis-a. Importantly, for the first time, we structurally validated the expression of Lewis-a in murine gastric mucosa. Finally, we demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding of H. pylori BabA adhesin, which is a recognized feature of pathogenicity. | |
dc.description.sponsorship | The authors thank Nuno Mendes for excellent technical support at the animal facility of IPATIMUP, University of Porto; Dr. Jacques Bara from the U-673 INSERM, CNRS, Paris, France for providing the PM7, 45M1 and 7LE antibodies; Dr Ingemar Carlstedt, University of Lund, Sweden for providing LUM6-3 and LUM5-1 antibodies and Dr. Ola Söderberg from the Uppsala Universitet, Sweden for support with the PLA experiments. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and the projects with the references FCOMP-01-0124-FEDER 028188 and FCOMP-01-0124-FEDER041276 (EXPL/CTM-BIO/0762/2013, PTDC/BBB-EBI/0786/2012 and PTDC/BBB-EBI/0567/2014). The authors acknowledge the support by Gastric Glyco Explorer Initial Training Network (Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). AM received an individual grant (SFRH/BPD/75871/2011) from FCT, POPH (Programa Operacional Potencial Humano) and FSE (Fundo Social Europeu) and acknowledges EMBO for a Short-Term Fellowship (EMBO ASTF 330-212). The resources provided by the Consortium for Functional Glycomics were funded by NIGMS-GM62116. TB is supported by grants from Vetenskapsrådet/VR, Cancerfonden, and the J.C. Kempe and Seth M. Kempe Memorial Foundation and this work was in part performed within the Umeå Centre for Microbial Research (UCMR), and the Biochemical Imaging Center Umeå (BICU). | |
dc.language.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.relation | info:eu-repo/grantAgreement/FCT/COMPETE/133784/PT | |
dc.relation | info:eu-repo/grantAgreement/FCT/COMPETE/125428/PT | |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F75871%2F2011/PT | |
dc.relation.ispartof | Scientific Reports, vol.6:25575 | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Adhesins, Bacterial/metabolism | |
dc.subject | Animals | |
dc.subject | Bacterial Adhesion | |
dc.subject | Fucosyltransferases/genetics | |
dc.subject | Fucosyltransferases/metabolism | |
dc.subject | Gastric Mucins/metabolism | |
dc.subject | Gastric Mucosa/metabolism | |
dc.subject | Glycosylation | |
dc.subject | Helicobacter Infections/metabolism | |
dc.subject | Helicobacter | |
dc.subject | Infections/microbiology | |
dc.subject | Helicobacter pylori/metabolism | |
dc.subject | Helicobacter pylori/physiology | |
dc.subject | Humans | |
dc.subject | Lewis Blood-Group System/metabolism | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.subject | Mucin 5AC/metabolism | |
dc.subject | Mucus/metabolism | |
dc.subject | Polysaccharides/metabolism | |
dc.subject | Protein Binding | |
dc.title | Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding | |
dc.type | Artigo em Revista Científica Internacional | |
dc.contributor.uporto | Instituto de Investigação e Inovação em Saúde | |
dc.identifier.doi | 10.1038/srep25575 | |
dc.relation.publisherversion | https://www.nature.com/articles/srep25575 | |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
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Magalhaes Scientific Rep 2016.pdf | 1.9 MB | Adobe PDF | View/Open |
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