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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: 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.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.

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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Related in: MedlinePlus

Adsorption of Factor H and FHR-1 to intact S. aureus.Cells of S. aureus strain H591 were incubated in human serum (A) or with purified Factor H (B). After extensive washing, bound proteins were eluted, separated by SDS-PAGE and analyzed by Western blotting using polyclonal Factor H antiserum. (A) In the eluted fraction (lane 2) polyclonal Factor H antiserum reacted with three bands of 150, 43 and 37 kDa representing Factor H, FHR-1β and FHR-1α, respectively. The same proteins were also identified in human serum (lane 3). (B) Purified Factor H bound to the bacteria and was detected in the elute fraction (lane 2). The mobility of the marker proteins is indicated. NHS, normal human serum.
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ppat-1000250-g001: Adsorption of Factor H and FHR-1 to intact S. aureus.Cells of S. aureus strain H591 were incubated in human serum (A) or with purified Factor H (B). After extensive washing, bound proteins were eluted, separated by SDS-PAGE and analyzed by Western blotting using polyclonal Factor H antiserum. (A) In the eluted fraction (lane 2) polyclonal Factor H antiserum reacted with three bands of 150, 43 and 37 kDa representing Factor H, FHR-1β and FHR-1α, respectively. The same proteins were also identified in human serum (lane 3). (B) Purified Factor H bound to the bacteria and was detected in the elute fraction (lane 2). The mobility of the marker proteins is indicated. NHS, normal human serum.

Mentions: In order to analyze binding of host complement regulators to S. aureus, strain H591 was incubated in human serum. After extensive washing bound proteins were eluted, separated by SDS-PAGE, transferred to a membrane and analyzed by Western blotting. This approach identified three bands of 150, 43 and 37 kDa, which represent Factor H, FHR-1β and FHR-1α, respectively (Figure 1A, lane 2). These proteins were absent in the final wash fraction, thus suggesting specific binding (Figure 1A, lane 1 and lane 2). The same proteins were also identified in human serum (Figure 1A, lane 3). When bacteria were incubated with purified Factor H binding of the purified protein was also detected in the eluted fraction (Figure 1B, lane 2).


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)

Adsorption of Factor H and FHR-1 to intact S. aureus.Cells of S. aureus strain H591 were incubated in human serum (A) or with purified Factor H (B). After extensive washing, bound proteins were eluted, separated by SDS-PAGE and analyzed by Western blotting using polyclonal Factor H antiserum. (A) In the eluted fraction (lane 2) polyclonal Factor H antiserum reacted with three bands of 150, 43 and 37 kDa representing Factor H, FHR-1β and FHR-1α, respectively. The same proteins were also identified in human serum (lane 3). (B) Purified Factor H bound to the bacteria and was detected in the elute fraction (lane 2). The mobility of the marker proteins is indicated. NHS, normal human serum.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1000250-g001: Adsorption of Factor H and FHR-1 to intact S. aureus.Cells of S. aureus strain H591 were incubated in human serum (A) or with purified Factor H (B). After extensive washing, bound proteins were eluted, separated by SDS-PAGE and analyzed by Western blotting using polyclonal Factor H antiserum. (A) In the eluted fraction (lane 2) polyclonal Factor H antiserum reacted with three bands of 150, 43 and 37 kDa representing Factor H, FHR-1β and FHR-1α, respectively. The same proteins were also identified in human serum (lane 3). (B) Purified Factor H bound to the bacteria and was detected in the elute fraction (lane 2). The mobility of the marker proteins is indicated. NHS, normal human serum.
Mentions: In order to analyze binding of host complement regulators to S. aureus, strain H591 was incubated in human serum. After extensive washing bound proteins were eluted, separated by SDS-PAGE, transferred to a membrane and analyzed by Western blotting. This approach identified three bands of 150, 43 and 37 kDa, which represent Factor H, FHR-1β and FHR-1α, respectively (Figure 1A, lane 2). These proteins were absent in the final wash fraction, thus suggesting specific binding (Figure 1A, lane 1 and lane 2). The same proteins were also identified in human serum (Figure 1A, lane 3). When bacteria were incubated with purified Factor H binding of the purified protein was also detected in the eluted fraction (Figure 1B, lane 2).

Bottom Line: 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.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.

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