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* University of Wuerzburg, Research Center for Infectious Diseases, Wuerzburg, Germany;
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany; and
Friedrich Schiller University, Jena, Germany
Pneumococcal surface protein C (PspC) of Streptococcus pneumoniae is a key virulence factor that mediates adhesion to host cells and immune evasion of the host complement. PspC binds the host immune and complement regulator factor H, which is composed of 20 short consensus repeats (SCR). This interaction contributes to pneumococcal virulence. In this study, we identified within the factor H protein two separate PspC binding regions, which were localized to SCR8–11 and SCR19–20, by using recombinant factor H deletion constructs for Western blotting assays and surface plasmon resonance studies. A detailed analysis of binding epitopes in these SCR by peptide spot arrays identified several linear binding regions within the sequences of SCR8–11 and SCR19–20. In addition, the factor H binding site was mapped within the pneumococcal PspC protein to a 121-aa-long stretch positioned in the N terminus (residues 38–158). Factor H attached to the surface of pneumococci via PspC significantly enhanced pneumococcal adherence to host epithelial and endothelial cells. This adhesion was specific and was blocked with a truncated N-terminal factor H-binding fragment of PspC. In conclusion, the acquisition of factor H by pneumococci via PspC occurs via two contact sites located in SCR8–11 and SCR19–20, and factor H attached to the surface of the pneumococcus promotes adhesion to both host epithelial and endothelial cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 479, Teilprojekt A7; to S.H.) and the Bundesministerium für Bildung und Forschung (CAPNETZ C8; to S.H.). V.A. is a recipient of a German Academic Exchange Service (DAAD) fellowship.
2 Address correspondence and reprint requests to Dr. Sven Hammerschmidt at the current address: Max von Pettenkofer Institute for Hygiene and Microbiology, Ludwig Maxmilians University Munich, Pettenkoferstrasse 9a, D-80336 Munich, Germany. E-mail address: hammerschmidt{at}mvp.uni.muenchen.de
3 Abbreviations used in this paper: PspC, pneumococcal surface protein C; CPS, capsular polysaccharide; FHL-1, factor H-like protein 1; GMFI, geometric mean fluorescence intensity; HBMEC, human brain-derived microvascular endothelial cell; pIgR, polymeric IgR; PVDF, polyvinylidene fluoride; SC, secretory component; SCR, short consensus repeat.
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