Novel Staphylococcal Glycosyltransferases SdgA and SdgB Mediate Immunogenicity and Protection of Virulence-Associated Cell Wall Proteins
Rattachement africain : nl, us, dk. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Novel Staphylococcal Glycosyltransferases SdgA and SdgB Mediate Immunogenicity and Protection of Virulence-Associated Cell Wall Proteins
- Date Crossref
- 10/10/2013
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Amsterdam UMC Location University of Amsterdam pays non établi dans la noticeÉtablissement de santé
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AIMM Therapeutics (Netherlands) pays non établi dans la noticeEntreprise
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University of California Division of Infectious Diseases pays non établi dans la noticeUniversité ou école supérieure
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Symphogen (Denmark) pays non établi dans la noticeEntreprise
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Inc. Genentech pays non établi dans la noticeEntreprise
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Academic Medical Center AIMM Therapeutics and Department of Cell Biology and Histology pays non établi dans la noticeÉtablissement de santé
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Proteomics Lab pays non établi dans la noticeStructure de recherche
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Symphogen A/S pays non établi dans la noticeInstitution
Amsterdam UMC Location University of Amsterdam, AIMM Therapeutics (Netherlands) et Division of Infectious Diseases — University of California, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.