The Staphylococcus aureus Protein Sbi Acts as a Complement Inhibitor and Forms a Tripartite Complex with Host Complement Factor H and C3b |
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| Authors: | Katrin Haupt Michael Reuter Jean van den Elsen Julia Burman Steffi H?lbich Julia Richter Christine Skerka Peter F Zipfel |
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| Institution: | 1. Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.; 2. Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.; 3. Friedrich Schiller University, Jena, Germany.;Dartmouth Medical School, United States of America |
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| Abstract: | The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1) from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG) as a ligand that interacts with Factor H by a—to our knowledge—new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite Sbi∶C3∶Factor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and β2-glycoprotein I and interferes with innate immune recognition. |
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