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PMID: 19112495 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

PLoS pathogens ·Vol. 4 ·No. 12 ·2008-12-00 ·Pages e1000250

Haupt K, Reuter M, van den Elsen J, Burman J, Hälbich S, Richter J, Skerka C, Zipfel PF

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.

MeSH Terms
Animals Bacterial Proteins/metabolism,pharmacology Carrier Proteins/metabolism,pharmacology Cells, Cultured Complement C3b/chemistry,metabolism Complement Factor H/chemistry,metabolism Complement Inactivating Agents/metabolism,pharmacology Host-Pathogen Interactions/immunology Humans Models, Biological Protein Binding Protein Multimerization Protein Structure, Tertiary/physiology Spodoptera Staphylococcal Infections/blood,immunology,metabolism Staphylococcus aureus/immunology,metabolism
Chemicals
Bacterial Proteins Carrier Proteins Complement Inactivating Agents Sbi protein, Staphylococcus aureus Complement C3b Complement Factor H
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Haupt Katrin
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
Reuter Michael
van den Elsen Jean
Burman Julia
Hälbich Steffi
Richter Julia
Skerka Christine
Zipfel Peter F
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Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000250
Published
2008-12-00
Epub
2008-00-26
Pages
e1000250
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC2602735
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.ppat.1000250 PMC Full Text View journal details
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