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- W2614737279 abstract "Staphylococcus aureus is a versatile human pathogen that has a remarkable ability to subvert host immune defences. This thesis investigates SSL10, a member of the staphylococcal superantigen-like protein (SSL) family. SSL10 was previously reported to interact with multiple aspects of the human immune system, including IgG, the complement system and the coagulation system, and thus is potentially important in S. aureus immune evasion. SSL10 binds IgG through its ??-grasp domain via an interface formed by ??10, ??11 and the loop in between the two strands, with residues F166, N168 and Y179 making the crucial contributions (Fig 3.11). Combined mutation of F166/N168/Y179 (SSL10-FNY) disabled the protein binding to IgG. Functional analysis of SSL10-FNY confirmed that the binding of SSL10 to IgG directly interferes with the association of C1q and Fc??R to the immunoglobulin, and thus inhibits the two major effector functions of IgG-mediated defence. SSL10-FNY retains the ability to inhibit complement and delay coagulation, indicating that IgG interaction and interference of the complement and coagulation cascades are distinct components of SSL10???s immune suppression. In addition to C1q, SSL10 further modulates the complement cascade by preventing the cleavage of C5 and reduces the production of C5a. The inter-domain interface and structural packing of SSL10 are important for this interaction, as mutations of a few inter-domain residues altered the complement inhibition profiles. SSL10 promoted the survival of S. aureus in human whole blood. The effect was related to the S. aureus induced coagulation. SSL10 did not induce coagulation itself, but accelerated plasma clotting in the presence of S. aureus. This property was not dependent on IgG binding although IgG interaction contributed substantially to the survival advantage provided by SSL10. Thus the distinct interactions of SSL10 with the immune system co-operate to enhance bacterial survival. SSL10 contributes to the synergistic actions of Staphylococcal virulence factors to maximize bacterial survival." @default.
- W2614737279 created "2017-05-26" @default.
- W2614737279 creator A5090801923 @default.
- W2614737279 date "2015-01-01" @default.
- W2614737279 modified "2023-09-24" @default.
- W2614737279 title "Characterization of Staphylococcal Superantigen-Like Protein 10 (SSL10)" @default.
- W2614737279 hasPublicationYear "2015" @default.
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