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*
Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;
Department of Cell and Molecular Biology, University of Lund, Lund, Sweden; and
Hans Knoell Institute for Natural Products Research, Jena, Germany
Streptococcus pneumoniae is an important cause of upper and lower respiratory tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which are particularly resistant to phagocytosis. On their surfaces the bacteria express the factor H-binding inhibitor of complement (Hic), a protein of the pneumococcal surface protein C family. Using radioligand binding, microtiter plate assays, surface plasmon resonance analysis, and recombinant constructs of factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8–11 in the middle part of factor H. This represents a novel microbial interaction region on factor H. The only other ligand known so far for SCRs 8–11 of factor H is C-reactive protein (CRP), an acute phase protein that binds to the pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8–11 region were different, however, because CRP did not inhibit the binding of Hic and required calcium for binding. Binding of factor H to Hic-expressing pneumococci promoted factor I-mediated cleavage of C3b and restricted phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack and opsonophagocytosis by recruiting functionally active factor H with the Hic surface protein. Hic binds to a previously unrecognized microbial interaction site in the middle part of factor H.
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A. Alitalo, T. Meri, T. Chen, H. Lankinen, Z.-Z. Cheng, T. S. Jokiranta, I. J. T. Seppala, P. Lahdenne, P. S. Hefty, D. R. Akins, et al. Lysine-Dependent Multipoint Binding of the Borrelia burgdorferi Virulence Factor Outer Surface Protein E to the C Terminus of Factor H J. Immunol., May 15, 2004; 172(10): 6195 - 6201. [Abstract] [Full Text] [PDF]
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F. Iannelli, D. Chiavolini, S. Ricci, M. R. Oggioni, and G. Pozzi Pneumococcal Surface Protein C Contributes to Sepsis Caused by Streptococcus pneumoniae in Mice Infect. Immun., May 1, 2004; 72(5): 3077 - 3080. [Abstract] [Full Text] [PDF]
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H. Jarva, J. Hellwage, T. S. Jokiranta, M. J. Lehtinen, P. F. Zipfel, and S. Meri The Group B Streptococcal {beta} and Pneumococcal Hic Proteins Are Structurally Related Immune Evasion Molecules That Bind the Complement Inhibitor Factor H in an Analogous Fashion J. Immunol., March 1, 2004; 172(5): 3111 - 3118. [Abstract] [Full Text] [PDF]
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P. Kraiczy, J. Hellwage, C. Skerka, H. Becker, M. Kirschfink, M. M. Simon, V. Brade, P. F. Zipfel, and R. Wallich Complement Resistance of Borrelia burgdorferi Correlates with the Expression of BbCRASP-1, a Novel Linear Plasmid-encoded Surface Protein That Interacts with Human Factor H and FHL-1 and Is Unrelated to Erp Proteins J. Biol. Chem., January 23, 2004; 279(4): 2421 - 2429. [Abstract] [Full Text] [PDF]
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B. Ren, A. J. Szalai, S. K. Hollingshead, and D. E. Briles Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface Infect. Immun., January 1, 2004; 72(1): 114 - 122. [Abstract] [Full Text] [PDF]
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L. Lu, M. E. Lamm, H. Li, B. Corthesy, and J.-R. Zhang The Human Polymeric Immunoglobulin Receptor Binds to Streptococcus pneumoniae via Domains 3 and 4 J. Biol. Chem., November 28, 2003; 278(48): 48178 - 48187. [Abstract] [Full Text] [PDF]
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C. E. Blue, G. K. Paterson, A. R. Kerr, M. Berge, J. P. Claverys, and T. J. Mitchell ZmpB, a Novel Virulence Factor of Streptococcus pneumoniae That Induces Tumor Necrosis Factor Alpha Production in the Respiratory Tract Infect. Immun., September 1, 2003; 71(9): 4925 - 4935. [Abstract] [Full Text] [PDF]
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T. G. Duthy, R. J. Ormsby, E. Giannakis, A. D. Ogunniyi, U. H. Stroeher, J. C. Paton, and D. L. Gordon The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15 Infect. Immun., October 1, 2002; 70(10): 5604 - 5611. [Abstract] [Full Text] [PDF]
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A. Alitalo, T. Meri, H. Lankinen, I. Seppala, P. Lahdenne, P. S. Hefty, D. Akins, and S. Meri Complement Inhibitor Factor H Binding to Lyme Disease Spirochetes Is Mediated by Inducible Expression of Multiple Plasmid-Encoded Outer Surface Protein E Paralogs J. Immunol., October 1, 2002; 169(7): 3847 - 3853. [Abstract] [Full Text] [PDF]
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