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

PLoS Pathogens

Jean van den Elsen¹  Julia Burman¹  Julia Richter²  Peter F. Zipfel²  Christine Skerka²  Michael Reuter²  Katrin Haupt²  Steffi Hälbich² 

[1] Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom;Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany

关键词: Complement system;    Complement inhibitors;    Immune serum;    Bacterial diseases;    Staphylococcus aureus;    Bacterial pathogens;    Binding analysis;    Complement activation;   

DOI  :  10.1371/journal.ppat.1000250

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY