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  1. Artikel ; Online: Novel method for detecting complement C3 deposition on Staphylococcus aureus.

    Wonfor, Toska / Li, Shuxian / Dunphy, Rhys W / Macpherson, Alex / van den Elsen, Jean / Laabei, Maisem

    Scientific reports

    2022  Band 12, Heft 1, Seite(n) 15766

    Abstract: The primary host response to Staphylococcus aureus infection occurs via complement. Complement is an elegant evolutionarily conserved system, playing essential roles in early defences by working in concert with immune cells to survey, label and destroy ... ...

    Abstract The primary host response to Staphylococcus aureus infection occurs via complement. Complement is an elegant evolutionarily conserved system, playing essential roles in early defences by working in concert with immune cells to survey, label and destroy microbial intruders and coordinate inflammation. Currently the exact mechanisms employed by S. aureus to manipulate and evade complement is not clear and is hindered by the lack of accurate molecular tools that can report on complement deposition on the bacterial surface. Current gold-standard detection methods employ labelled complement-specific antibodies and flow cytometry to determine complement deposited on bacteria. These methods are restricted by virtue of the expression of the S. aureus immunoglobulin binding proteins, Protein A and Sbi. In this study we describe the use of a novel antibody-independent C3 probe derived from the staphylococcal Sbi protein, specifically Sbi-IV domain. Here we show that biotin-labelled Sbi-IV interacts specifically with deposited C3 products on the staphylococcal surface and thus can be used to measure complement fixation on wild-type cells expressing a full repertoire of immune evasion proteins. Lastly, our data indicates that genetically diverse S. aureus strains restrict complement to different degrees suggesting that complement evasion is a variable virulence trait among S. aureus isolates.
    Mesh-Begriff(e) Bacterial Proteins ; Biotin/metabolism ; Complement C3/metabolism ; Humans ; Protein Binding ; Staphylococcal Infections ; Staphylococcus aureus/metabolism
    Chemische Substanzen Bacterial Proteins ; Complement C3 ; Biotin (6SO6U10H04)
    Sprache Englisch
    Erscheinungsdatum 2022-09-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-20098-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Staphylococcal Complement Evasion Protein Sbi Stabilises C3d Dimers by Inducing an N-Terminal Helix Swap.

    Dunphy, Rhys W / Wahid, Ayla A / Back, Catherine R / Martin, Rebecca L / Watts, Andrew G / Dodson, Charlotte A / Crennell, Susan J / van den Elsen, Jean M H

    Frontiers in immunology

    2022  Band 13, Seite(n) 892234

    Abstract: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    Mesh-Begriff(e) Animals ; Bacterial Proteins ; Carrier Proteins/metabolism ; Disulfides/metabolism ; Rats ; Staphylococcus/metabolism ; Staphylococcus aureus
    Chemische Substanzen Bacterial Proteins ; Carrier Proteins ; Disulfides
    Sprache Englisch
    Erscheinungsdatum 2022-05-25
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.892234
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Insights Into the Structure-Function Relationships of Dimeric C3d Fragments.

    Wahid, Ayla A / Dunphy, Rhys W / Macpherson, Alex / Gibson, Beth G / Kulik, Liudmila / Whale, Kevin / Back, Catherine / Hallam, Thomas M / Alkhawaja, Bayan / Martin, Rebecca L / Meschede, Ingrid / Laabei, Maisem / Lawson, Alastair D G / Holers, V Michael / Watts, Andrew G / Crennell, Susan J / Harris, Claire L / Marchbank, Kevin J / van den Elsen, Jean M H

    Frontiers in immunology

    2021  Band 12, Seite(n) 714055

    Abstract: Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we ... ...

    Abstract Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future.
    Mesh-Begriff(e) Complement C3/chemistry ; Complement C3/immunology ; Complement C3d/chemistry ; Complement C3d/immunology ; Humans ; Lymphocyte Activation/immunology ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Multimerization ; Proteolysis ; Recombinant Proteins/chemistry ; Structure-Activity Relationship
    Chemische Substanzen Complement C3 ; Recombinant Proteins ; Complement C3d (80295-45-0)
    Sprache Englisch
    Erscheinungsdatum 2021-08-09
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.714055
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

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