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

Haupt K, Reuter M, van den Elsen J, Burman J, Hälbich S, Richter J, Skerka C, Zipfel PF - PLoS Pathog. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.

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.

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Localization of the Sbi binding regions within Factor H.The indicated Factor H deletion constructs were immobilized to the surface of a microtiter plate and the Sbi deletion constructs together with C3b were added. Binding was assayed by ELISA using polyclonal Factor H antiserum. SCRs 15–20 and SCRs 19–20 bound to Sbi-E and Sbi-III/IV but not to Sbi-I. The additional Factor H deletion mutants did not bind to Sbi.
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ppat-1000250-g006: Localization of the Sbi binding regions within Factor H.The indicated Factor H deletion constructs were immobilized to the surface of a microtiter plate and the Sbi deletion constructs together with C3b were added. Binding was assayed by ELISA using polyclonal Factor H antiserum. SCRs 15–20 and SCRs 19–20 bound to Sbi-E and Sbi-III/IV but not to Sbi-I. The additional Factor H deletion mutants did not bind to Sbi.

Mentions: To further characterize this novel type of Factor H acquisition with C3, we decided to identify the Factor H domains that are involved in this interaction. Factor H deletion constructs were immobilized and used in an ELISA experiment. In the presence of C3b, Sbi-E and Sbi-III/IV, but not to Sbi-I bound to immobilized Factor H SCRs 19–20 and SCRs 15–20 (Figure 6, columns 5 and 6). In addition Sbi-I did not bind to any Factor H deletion construct. Thus the Sbi binding site was localized within the C-terminal surface binding region of Factor H, within SCRs 19–20 and is restricted to Sbi domains three and four.


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

Haupt K, Reuter M, van den Elsen J, Burman J, Hälbich S, Richter J, Skerka C, Zipfel PF - PLoS Pathog. (2008)

Localization of the Sbi binding regions within Factor H.The indicated Factor H deletion constructs were immobilized to the surface of a microtiter plate and the Sbi deletion constructs together with C3b were added. Binding was assayed by ELISA using polyclonal Factor H antiserum. SCRs 15–20 and SCRs 19–20 bound to Sbi-E and Sbi-III/IV but not to Sbi-I. The additional Factor H deletion mutants did not bind to Sbi.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2602735&req=5

ppat-1000250-g006: Localization of the Sbi binding regions within Factor H.The indicated Factor H deletion constructs were immobilized to the surface of a microtiter plate and the Sbi deletion constructs together with C3b were added. Binding was assayed by ELISA using polyclonal Factor H antiserum. SCRs 15–20 and SCRs 19–20 bound to Sbi-E and Sbi-III/IV but not to Sbi-I. The additional Factor H deletion mutants did not bind to Sbi.
Mentions: To further characterize this novel type of Factor H acquisition with C3, we decided to identify the Factor H domains that are involved in this interaction. Factor H deletion constructs were immobilized and used in an ELISA experiment. In the presence of C3b, Sbi-E and Sbi-III/IV, but not to Sbi-I bound to immobilized Factor H SCRs 19–20 and SCRs 15–20 (Figure 6, columns 5 and 6). In addition Sbi-I did not bind to any Factor H deletion construct. Thus the Sbi binding site was localized within the C-terminal surface binding region of Factor H, within SCRs 19–20 and is restricted to Sbi domains three and four.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.

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.

Show MeSH
Related in: MedlinePlus