title: The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.
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 SbiratioC3ratioFactor 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 beta(2)-glycoprotein I and interferes with innate immune recognition.
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Haupt
authors.forename: Michael
authors.initials: M
authors.lastname: Reuter
authors.forename: Jean
authors.initials: J
authors.lastname: van den Elsen
authors.forename: Julia
authors.initials: J
authors.lastname: Burman
authors.forename: Steffi
authors.initials: S
authors.lastname: Hälbich
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003179:Complement C3b / Q000737:chemistry / Q000378:metabolism*; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism*; D051056:Complement Inactivating Agents / Q000378:metabolism / Q000494:pharmacology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary / Q000502:physiology; D018411:Spodoptera; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D051056:Complement Inactivating Agents; C112405:Sbi protein, Staphylococcus aureus; D003179:Complement C3b; D017242:Complement Factor H