The <em>Staphylococcus aureus</em> Protein Sbi Acts as a Complement Inhibitor and Forms a Tripartite Complex with Host Complement Factor H and C3b

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.革兰氏阳性菌金黄色葡萄球菌（Staphylococcus aureus）与其他病原体类似，可结合人血清中的补体因子H（Factor H）及补体因子H相关蛋白1（Factor H related protein 1, FHR-1）。本研究鉴定出分泌蛋白Sbi（Staphylococcus aureus binder of IgG，金黄色葡萄球菌IgG结合蛋白）是一类据我们所知通过全新相互作用模式结合补体因子H的配体。补体因子H可与Sbi结合，并结合C3b或C3d，形成三元复合物Sbi∶C3∶补体因子H。研究表明，C3的类型会影响该复合物的稳定性；表面等离子体共振（surface plasmon resonance）实验显示，相较于C3b或C3，与Sbi结合的C3d复合物稳定性更高。作为该三元复合物的组成部分，补体因子H保持功能活性，并展现出补体调节活性。Sbi通过募集补体因子H与C3b，可作为强效补体抑制剂，能够抑制人血清及其他物种血清中补体旁路途径介导的兔红细胞裂解。综上，Sbi是一种多功能细菌蛋白，可结合宿主补体成分补体因子H、C3，以及免疫球蛋白G（Immunoglobulin G, IgG）与β2-糖蛋白I（β2-glycoprotein I），并干扰先天免疫识别过程。