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Staphylococcal Complement Inhibitors: Biological Functions, Recognition of Complement Components, and Potential Therapeutic Implications

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Current Topics in Complement II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 632))

Abstract

It has been known for quite some time that many pathogenic microorganisms are capable of specifically attenuating or bypassing complement-mediated immune responses. Over the last several years, our understanding of the complement evasion mechanisms utilized by pathogens has increased precipitously through the study of the virulent bacterium Staphylococcus aureus. The combination of structural and functional characterization of S. aureus-derived complement inhibitors has revealed new mechanisms of complement regulation. Study of these proteins may also hold important clues into the design and optimization of long-awaited therapeutics that specifically and effectively block the complement activation and amplification cascades.

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References

  • Al-Shangiti, A.M., Naylor, C.E., Nair, S.P., Briggs, D.C., Henderson, B. and Chain, B.M. (2004) Structural relationships and cellular tropism of Staphylococcal supernantigen-like proteins. Infect. Immun. 72, 4261–4270

    Article  PubMed  CAS  Google Scholar 

  • Bredius, R.G., Driedijk, P.C., Schouten, M.F., Weening, R.S. and Out, T.A. (1992) Compelment activation by polyclonal immunoglobulin G1 and G2 antibodies against Staphylococcus aureus. , Haemophilus influenzae type B, and tetanus toxoid Infect. Immun. 60, 4838–4847

    PubMed  CAS  Google Scholar 

  • Cedergren, L., Andersson, R., Jansson, B., Uhlen, M. and Nilsson, B. (1993) Mutational analysis of the interaction between Staphylococcal protein A and human IgG1. Protein Eng. 6, 441–448

    Article  PubMed  CAS  Google Scholar 

  • Chavakis, T., Wiechmann, K., Preissner, K.T. and Herrmann, M. (2005) Staphylococcus aureus. interactions with the endothelium: the role of bacterial “Secreteable Expanded Repertoire Adhesive Molecules”(SERAM) in disturbing host defense systems Thromb. Haemost. 94, 278–285

    PubMed  CAS  Google Scholar 

  • Chavakis, T., Preissner, K.T. and Herrmann, M. (2007) The anti-inflammatory activities of Staphylococcus aureus. Trends Immunol. 28, 408–418

    Article  PubMed  CAS  Google Scholar 

  • Chen, H., Schuster, M.C., Sfyroera, G., Geisbrecht, B.V. and Lambris, J.D. (2008) Solution insights into the structure of the Efb/C3 complement inhibitory complex as revealed by lysine acetylation nand mass spectrometry. J. Am. Soc. Mass. Spectrom. 19, 55–65

    Article  PubMed  Google Scholar 

  • Cunnion, K.M., Lee, J.C. and Frank, M.M. (2001) Capsule production and growth phase influence binding of complement to Staphylococcus aureus. Infect. Immun. 69, 6796–6803

    Article  PubMed  CAS  Google Scholar 

  • Cunnion, K.M., Hair, P.S. and Buescher, E. (2004) Cleavage of complement C3b to iC3b on the surface of Staphylococcus aureus. is mediated by serum complement factor I Infect. Immun. 72, 2858–2863

    Article  PubMed  CAS  Google Scholar 

  • Cunnion, K.M., Buescher, E.S. and Hair, P.S. (2005) Serum complement factor I decreases Staphylococcus aureus. phagocytosis J. Lab. Clin. Med. 146, 279–286

    Article  PubMed  CAS  Google Scholar 

  • de Haas, C.J., Veldkamp, K.E., Peschel, A., Weerkamp, F., van Wamel, W.J., Heezius, E.C., Poppelier, M.J., van Kessel, K.P. and van Strijp, J.A. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus. , a bacterial antiinflammatory agent J. Exp. Med. 199, 687–695

    Article  PubMed  CAS  Google Scholar 

  • Foster, T.J. (2005) Immune evasion by Staphylococci. Nat. Rev. Microbiol. 3, 948–958

    Article  PubMed  CAS  Google Scholar 

  • Frank, M.M. (2001) Annihilating host defense. Nat. Med. 7, 1285–1286

    Article  PubMed  CAS  Google Scholar 

  • Geisbrecht, B.V., Hamaoka, B.Y., Perman, B., Zemla, A. and Leahy, D.J. (2005) The crystal structures of EAP domains from Staphylococcus aureus. reveal an unexpected homology to bacterial superantigens J. Biol. Chem. 280, 17243–17250

    Article  PubMed  CAS  Google Scholar 

  • Gouda, H., Torigoe, H., Saito, A., Sato, M., Arata, Y. and Shimada, I. (1992) Three-dimensional solution structure of the B domain of Staphylococcal protein A: comparisons of the solution and crystal structures. Biochemistry 31, 9665–9672

    Article  PubMed  CAS  Google Scholar 

  • Gros, P., Milder, F.J. and Janssen, B.J.C. (2008) Complement driven by conformational changes. Nat. Rev. Immunol. 8, 48–58

    Article  PubMed  CAS  Google Scholar 

  • Haas, P.J., de Haas, C.J., Poppelier, M.J., van Kessel, K.P., van Strijp, J.A., Dijkstra, K., Scheek, R.M., Fan, H., Kruijtzer, J.A., Liskamp, R.M. and Kemmink, J. (2005) The structure of the C5a receptor-blocking domain of chemotaxis inhibitory protein of Staphylococcus aureus. is related to a group of immune evasive molecules J. Mol. Biol. 353, 859–872

    Article  PubMed  CAS  Google Scholar 

  • Hammel, M., Sfyroera, G., Pyrpassopoulos, S., Ricklin, D., Ramyar, K.X., Pop, M., Jin, Z., Lambris, J.D. and Geisbrecht, B.V. (2007a) Characterization of Ehp: a secreted complement inhibitory protein from Staphylococcus aureus. J. Biol. Chem. 202, 30051–30061

    Article  Google Scholar 

  • Hammel, M., Sfyroera, G., Ricklin, D., Magotti, P., Lambris, J.D. and Geisbrecht, B.V. (2007b) A structural basis for complement inhibition by Staphylococcus aureus. Nat. Immunol. 8, 430–437

    Article  CAS  Google Scholar 

  • Janssen, B.J.C., Huizinga, E.G., Raaijmakers, H.C.A., Roos, A., Daha, M.R., Ekdahl-Nilsson, K., Nilsson, B. and Gros, P. (2005) Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437, 505–511

    Article  PubMed  CAS  Google Scholar 

  • Janssen, B.J.C., Christodoulidou, A., McCarthy, A., Lambris, J.D. and Gros, P. (2006) Structure of C3b reveals conformational changes underlying complement activity. Nature 444, 213–216

    Article  PubMed  CAS  Google Scholar 

  • Jongerius, I., Köhl, J., Pandey, M.K., Ruyken, M., van Kessel, K.P., van Strijp, J.A. and Rooijakkers, S.H. (2007) Staphylococcal complement evasion by various convertase-blocking molecules J. Exp. Med. 204, 2461–2471

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki, A., Takada, H., Kotani, S., Inai, S., Nagaki, K., Matsumoto, M., Yokogawa, K., Kawata, S., Kusumoto, S. and Shiba, T. (1987) Activation of the human complement cascade by bacterial cell walls, peptidoglycans, water-soluble peptidoglycan components, and synthetic muramylpeptides – studies on active components and structural requirements. Microbiol. Immunol. 31, 551–569

    PubMed  CAS  Google Scholar 

  • Lambris, J.D., Ricklin, D. and Geisbrecht, B.V. (2008) Complement evasion by human pathogens. Nat. Rev. Microbiol. 6, 132–142

    Article  PubMed  CAS  Google Scholar 

  • Langley, R., Wines, B., WIlloughby, N., Basu, I., Proft, T. and Fraser, J.D. (2005) The Staphylococcal superantigen-like protein 7 binds IgA and complement C5 and inhibits IgA-FcaRI binding and serum killing of bacteria. J. Immunol. 174, 2926–2933

    PubMed  CAS  Google Scholar 

  • Lee, L.Y.L., Hook, M., Haviland, D., Wetsel, R.A., Yonter, E.O., Syribeys, P., Vernachio, J. and Brown, E.L. (2004a) Inhibition of complement activation by a secreted Staphylococcus aureus. protein J. Infect. Dis. 190, 571–579

    Article  CAS  Google Scholar 

  • Lee, L.Y.L., Liang, X., Hook, M. and Brown, E.L. (2004b) Identification and characterization of the C3 binding domain of the Staphylococcus aureus. extracellular fibrinogen-binding protein (Efb) J. Biol. Chem. 279, 50710–50716

    Article  CAS  Google Scholar 

  • Lowy, F.D. (1998) Staphylococcus aureus. infections N. Engl. J. Med. 339, 520–532

    Article  PubMed  CAS  Google Scholar 

  • Morikis, D. and Lambris, J.D. (2005) Structure, Dynamics, Activity, and Function of Compstatin and Design of More Potent Analogs. Taylor and Francis, Boca Raton, FL

    Google Scholar 

  • Nagar, B., Jones, R.G., Diefenbach, R.J., Isenman, D.E. and Rini, J.M. (1998) X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2. Science 280, 1277–1281

    Article  PubMed  CAS  Google Scholar 

  • Neth, O., Jack, D.L., Johnson, M., Klein, N.J. and Turner, M.W. (2002) Enhancement of complement activation and opsonophagocytosis by complexes of mannose-binding lectin with mannose-binding lectin-associated serine protease after binding to Staphylococcus aureus. J. Immunol. 169, 4430–4436

    PubMed  CAS  Google Scholar 

  • Nguyen, T., Ghebrehiwet, B. and Peerschke, E.I.B. (2000) Staphylococcus aureus. protein A recognizes platelet gC1qR/p33: a nove mechanism for Staphylococcal interactions with platelets Infect. Immun. 68, 2061–2068

    Article  PubMed  CAS  Google Scholar 

  • O’Riordan, K. and Lee, J.C. (2004) Staphylococcus aureus. capsular polysaccharides Clin. Microbiol. Rev. 17, 218–234

    Article  PubMed  Google Scholar 

  • Peterson, P.K., Kim, Y., Wilkinson, B.J., Schmeling, D., Michael, A.F. and Quie, P.G. (1978) Dichotomy between opsonization and serum complement activation by encapsulated Staphylococci. Infect. Immun. 20, 770–775

    PubMed  CAS  Google Scholar 

  • Postma, B., Poppelier, M.J., van Galen, J.C., Prossnitz, E.R., van Strijp, J.A., de Haas, C.J. and van Kessel, K.P. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus. binds specifically to the C5a and formylated peptide receptor J. Immunol. 172, 6994–7001

    PubMed  CAS  Google Scholar 

  • Postma, B., Kleibeuker, W., Poppelier, M.J., Boonstra, M., van Kessel, K.P., van Strijp, J.A. and de Haas, C.J. (2005) Residues 10-18 within the C5a receptor N terminus compose a binding domain for chemotaxis inhibitory protein of Staphylococcus aureus. J. Biol. Chem. 280, 2020–2027

    Article  PubMed  CAS  Google Scholar 

  • Ricklin, D. and Lambris, J.D. (2007) Complement-targeted therapeutics. Nat. Biotechnol. 25, 1265–1275

    Article  PubMed  CAS  Google Scholar 

  • Rooijakkers, S.H., Ruyken, M., Roos, A., Daha, M.R., Presanis, J.S., Sim, R.B., van Wamel, W.J., van Kessel, K.P. and van Strijp, J.A. (2005a) Immune evasion by a Staphylococcal complement inhibitor that acts on C3 convertases. Nat. Immunol. 6, 920–927

    Article  CAS  Google Scholar 

  • Rooijakkers, S.H., van Kessel, K.P. and van Strijp, J.A. (2005b) Staphylococcal innate immune evasion. Trends Microbiol. 13, 596–601

    Article  CAS  Google Scholar 

  • Rooijakkers, S.H.M., Milder, F.J., Bardoel, B.W., Ruyken, M., van Strijp, J.A.G. and Gros, P. (2007) Staphylococcal complement inhibitor: structure and active sites. J. Immunol. 179, 2989–2998

    PubMed  CAS  Google Scholar 

  • Sahu, A. and Lambris, J.D. (2001) Structure and biology of complement protein 3, a connecting link between innate and acquired immunity. Immunol. Rev. 180, 35–48

    Article  PubMed  CAS  Google Scholar 

  • Verbrugh, H.A., van Dijk, W.C., Peters, R., van der Tol, M.E. and Verhoef, J. (1979) The role of Staphylococcus aureus. cell-wall peptidoglycan, teichoic acid, and protein A in the processes of complement activation and opsonization Immunology 37, 615–621

    PubMed  CAS  Google Scholar 

  • Verbrugh, H.A., Peterson, P.K., Nguyen, B.-Y.T., Sisson, S.P. and Kim, Y. (1982) Opsonization of encapsulated Stapylococcus aureus. : the role of specific antibody and complement J. Immunol. 129, 1681–1687

    PubMed  CAS  Google Scholar 

  • Wilkinson, B.J., Kim, Y., Peterson, P.K., Quie, P.G. and Michael, A.F. (1978) Activation of complement by cell surface components of Staphylococcus aureus. Infect. Immun. 20, 388–392

    PubMed  CAS  Google Scholar 

  • Zhang, L., Jacobsson, K., Vasi, J., Lindberg, M. and Frykberg, L. (1998) A second IgG-binding protein in Staphylococcus aureus. Microbiology 144, 985–991

    Article  PubMed  CAS  Google Scholar 

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Geisbrecht, B.V. (2008). Staphylococcal Complement Inhibitors: Biological Functions, Recognition of Complement Components, and Potential Therapeutic Implications. In: Lambris, J. (eds) Current Topics in Complement II. Advances in Experimental Medicine and Biology, vol 632. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78952-1_16

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