The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b

PLoS Pathog. 2008 Dec;4(12):e1000250. doi: 10.1371/journal.ppat.1000250. Epub 2008 Dec 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology*
  • Cells, Cultured
  • Complement C3b / chemistry
  • Complement C3b / metabolism*
  • Complement Factor H / chemistry
  • Complement Factor H / metabolism*
  • Complement Inactivating Agents / metabolism
  • Complement Inactivating Agents / pharmacology*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Models, Biological
  • Protein Binding
  • Protein Multimerization*
  • Protein Structure, Tertiary / physiology
  • Spodoptera
  • Staphylococcal Infections / blood
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / metabolism

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Complement Inactivating Agents
  • Sbi protein, Staphylococcus aureus
  • Complement C3b
  • Complement Factor H