Skip to main content
SpringerLink
Log in

Binding of human complement regulators FHL-1 and factor H to CRASP-1 orthologs of Borrelia burgdorferi

  • Original Article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

The complement regulator-acquiring surface protein (CRASP)-1 is a member of the paralogous gene family gbb54 and the dominant FHL-1 and factor H binding protein of Borrelia burgdorferi sensu stricto (s.s.). It was shown recently that expression of BbCRASP-1 directly correlates with serum resistance of B. burgdorferi s.s. isolates. In the present study we have elucidated the putative potential of other members of the gbb54 paralogous family, including orthologs ZSA66, ZSA69, ZSA70, ZSA71, ZSA72 and ZSA73 of the European B. burgdorferi s.s. strain ZS7, to bind human FHL-1 and factor H. In spite of their overall similarity in protein sequence, between 47% and 67%, and the fact that the C-terminal region of ZSA69 shows 70% similarity with BbCRASP-1, none of the orthologous proteins was able to bind human FHL-1 and/or factor H. BbCRASP-1 is the only member of the paralogous gene family gbb54 that binds to human complement regulators, supporting the notion that BbCRASP-1 plays a critical role in evasion of complement by B. burgdorferi s.s. and thus may be helpful in the development of novel therapeutic strategies against Lyme borreliosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Steere AC, Coburn J, Glickstein L (2004) The emergence of Lyme disease. J Clin Invest 113: 1093–1101

    Article  CAS  PubMed  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (2004) Lyme disease – United States, 2001–2002. MMWR Morb. Mortal Wkly Rep 53: 365–369

    Google Scholar 

  • Embers ME, Ramamoorthy R, Philipp MT (2004) Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease. Microbes Infect 6: 312–318

    Article  PubMed  Google Scholar 

  • Kraiczy P, Skerka S, Kirschfink M, Zipfel PF, Brade V (2001) Mechanism of complement resistance of pathogenic Borrelia burgdorferi isolates. Intern Immunopharmcol 1: 393–401

    Article  CAS  Google Scholar 

  • Kurtenbach K, De Michaelis S, Etti S, Schäfer SM, Sewell H-S, Brade V, et al (2002) Host association of Borrelia burgdorferi – the key role of host complement. Trends Microbiol 10: 74–79

    Article  CAS  PubMed  Google Scholar 

  • Zipfel PF, Skerka C, Hellwage J, Jokiranta TS, Meri S, Brade V, et al (2002) Factor H family proteins: on complement, microbes and human diseases. Biochem Soc Trans 30: 971–978

    Article  CAS  PubMed  Google Scholar 

  • Kühn S, Skerka C, Zipfel PF (1995) Mapping of the complement regulatory domains in the human factor Hlike protein 1 and in factor H. J Immunol 155: 5663–5670

    PubMed  Google Scholar 

  • Zipfel PF, Skerka C (1999) FHL-1/reconectin: a human complement and immune regulator with cell-adhesive function. Immunol Today 20: 135–140

    Article  CAS  PubMed  Google Scholar 

  • Kühn S, Zipfel PF (1996) Mapping of the domains required for decay acceleration activity of the human factor H-like protein 1 and factor H. Eur J Immunol 26: 2383–2387

    PubMed  Google Scholar 

  • Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1977) Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein β1H for cleavage of C3b and C4b in solution. J Exp Med 146: 257–270

    Article  CAS  PubMed  Google Scholar 

  • Whaley K, Ruddy R (1976) Modulation of the alternative complement pathways by β1H globulin. J Exp Med 144: 1147–1163

    Article  CAS  PubMed  Google Scholar 

  • Horstmann RD, Sievertsen HJ, Knobloch J, Fischetti VA (1988) Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci USA 85: 1657–1661

    Article  CAS  PubMed  Google Scholar 

  • Johnsson E, Berggard K, Kotarsky H, Hellwage J, Zipfel PF, Sjöbring U, et al (1998) Role of the hypervariable region in streptococcal M proteins: binding of a human complement inhibitor. J Immunol 161: 4894–4901

    CAS  PubMed  Google Scholar 

  • Neeleman C, Geelen SP, Aerts PC, Daha MR, Mollnes TE, Roord JJ, et al (1999) Resistance to both complement activation and phagocytosis in type 3 pneumococci is mediated by the binding of complement regulatory protein factor H. Infect Immun 67: 4517–4524

    CAS  PubMed  Google Scholar 

  • Ram S, McQuillen D, Gulait S, Elkins C, Pangburn MK, Rice PA (1998) Binding of Complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. J Exp Med 188: 671–680

    Article  CAS  PubMed  Google Scholar 

  • Ram S, Sharma AK, Simpson SC, Gulati DS, McQuillen D, Pangburn MK, et al (1998) A novel sialic acid binding site on Factor H mediates serum resistance of sialylated Neisseria gonorrhoeae. J Exp Med 187: 743–752

    Article  CAS  PubMed  Google Scholar 

  • Ram S, Mackinnon FG, Gulati S, McQuillen DP, Vogel U, Frosch M, Elkins C, et al (1999) The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis. Mol Immunol 36: 915–928

    Article  CAS  PubMed  Google Scholar 

  • Meri T, Hartmann A, Lenk D, Eck R, Würzner R, Hellwage J, et al (2002) The yeast Candida albicans binds complement regulators factor H and FHL-1. Infect Immun 70: 5185–5192

    Article  CAS  PubMed  Google Scholar 

  • Meri T, Murgia R, Stefanel P, Meri S, Cinco M (2005) Regulation of complement activation at the C3-level by serum resistant leptospires. Microb Pathog 39: 139–147

    Article  CAS  PubMed  Google Scholar 

  • McDowell JV, Lankford J, Stamm L, Sadlon T, Gordon DL, Marconi RT (2005) Demonstration of factor H-like protein 1 binding to Treponema denticola, a pathogen associated with periodontal disease in humans. Infect Immun 73: 7126–7132

    Article  CAS  PubMed  Google Scholar 

  • McDowell JV, Tran E, Hamilton D, Wolfgang J, Miller K, Marconi RT (2003) Analysis of the ability of spirochete species associated with relapsing fever, avian borreliosis, and epizootic bovine abortion to bind factor H and cleave C3b. J Clin Microbiol 41: 3905–3910

    Article  CAS  PubMed  Google Scholar 

  • Areschoug T, Stålhammar-Carlemann M, Karlsson I, Lindahl G (2002) Streptococcal β protein has a separate binding site for human factor H and IgGA-Fc. J Biol Chem 277: 12642–12648

    Article  CAS  PubMed  Google Scholar 

  • Kotarsky H, Hellwage J, Johnsson E, Skerka C, Svensson HG, Lindahl G, et al (1998) Identification of a domain in human factor H and factor H-like protein-1 required for the interaction with streptococcal M proteins. J Immunol 160: 3349–3354

    CAS  PubMed  Google Scholar 

  • Pandiripally V, Gregory E, Cue D (2002) Acquisition of regulators of complement activation by Streptococcus Serotype M1. Infect Immun 70: 6206–6214

    Article  CAS  PubMed  Google Scholar 

  • Janulczyk R, Iannelli F, Sjöholm AG, Pozzi G, Björck L (2000) Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function. J Biol Chem 47: 37257–37263

    Article  Google Scholar 

  • Jarva H, Janulczyk R, Hellwage J, Zipfel PF, Björck L, Meri S (2002) Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8–11 of factor H. J Immunol 168: 1886–1894

    CAS  PubMed  Google Scholar 

  • Jarva H, Hellwage J, Jokiranta TS, Lehtinen MJ, Zipfel PF, Meri S (2004) The group B streptococcal β and pneumococcal Hic proteins are structurally related immune evasion molecules that bind the complement inhibitor factor H in an analogous fashion. J Immunol 172: 3111–3118

    CAS  PubMed  Google Scholar 

  • Hovis KM, McDowell JV, Griffin L, Marconi RT (2004) Identification and characterization of a linear-plasmid-encoded factor H-binding protein (FhbA) of the relapsing fever spirochete Borrelia hermsii. J Bacteriol 186: 2612–2618

    Article  CAS  PubMed  Google Scholar 

  • Kraiczy P, Skerka C, Kirschfink M, Brade V, Zipfel PF (2001) Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and factor H. Eur. J Immunol 31: 1674–1684

    Article  CAS  PubMed  Google Scholar 

  • Kraiczy P, Skerka C, Brade V, Zipfel PF (2001) Further characterization of complement regulator-acquiring surface proteins of Borrelia burgdorferi. Infect Immun 69: 7800–7809

    Article  CAS  PubMed  Google Scholar 

  • Kraiczy P, Skerka C, Zipfel PF, Brade V (2002) Complement regulator-acquiring surface proteins of Borrelia burgdorferi: a new protein family involved in complement resistance. Wien Klin Wochenschr 114: 568–573

    CAS  PubMed  Google Scholar 

  • Wallich R, Pattathu J, Kitiratschky V, Brenner C, Zipfel PF, Brade V, et al (2005) Identification and functional characterization of complement regulator-acquiring surface protein (CRASP)-1 of the Lyme disease spirochetes Borrelia afzelii and Borrelia garinii. Infect Immun 73: 2351–2359

    Article  CAS  PubMed  Google Scholar 

  • Alitalo A, Meri T, Comstedt P, Jeffery L, Tornberg J, Lankinen H, et al (2005) Expression of complement factor H binding immunoevasion proteins in Borrelia garinii isolated from patients with neuroborreliosis. Eur J Immunol 35: 3043–3053

    Article  CAS  PubMed  Google Scholar 

  • Kraiczy P, Hartmann K, Hellwage J, Skerka C, Kirschfink M, Brade V, et al (2004) Immunological characterization of the complement regulator factor H-binding CRASP and Erp proteins of Borrelia burgdorferi. Int J Med Microbiol 293 [Suppl 36]: 152–157

    CAS  PubMed  Google Scholar 

  • Kraiczy P, Hellwage J, Skerka C, Kirschfink M, Brade V, Zipfel PF, et al (2003) Immune evasion of Borrelia burgdorferi: mapping of a complement inhibitor factor H-binding site of BbCRASP-3, a novel member of the Erp protein family. Eur J Immunol 33: 697–707

    Article  CAS  PubMed  Google Scholar 

  • Kraiczy P, Hellwage J, Skerka C, Becker H, Kirschfink M, Simon MM, et al (2004) Characterization of BbCRASP-1, the dominant factor H and FHL-1 binding protein of Borrelia burgdorferi. J Biol Chem 279: 2421–2429

    Article  CAS  PubMed  Google Scholar 

  • Stevenson B, El-Hage N, Hines M, Miller JC, Babb K (2002) Differential binding to host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes. Infect Immun 70: 491–497

    Article  CAS  PubMed  Google Scholar 

  • Metts MS, McDowell JV, Theisen M, Hansen PR, Marconi RT (2003) Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice. Infect Immun 71: 3587–3596

    Article  CAS  PubMed  Google Scholar 

  • Alitalo A, Meri T, Lankinen H, Seppälä IJT, Lahdenne P, Hefty PS, et al (2002) 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 169: 3847–3853

    CAS  PubMed  Google Scholar 

  • Alitalo A, Meri T, Chen T, Lankinen H, Cheng Z-Z, Jokiranta TS, et al (2004) Lysine-dependent multipoint binding of the Borrelia burgdorferi virulence factor outer surface protein E to the C terminus of factor H. J Immunol 172: 6195–6201

    CAS  PubMed  Google Scholar 

  • Hellwage J, Meri T, Heikkilä A, Panelius J, Lahdenne P, Seppälä IJT, et al (2001) The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J Biol Chem 276: 8427–8435

    Article  CAS  PubMed  Google Scholar 

  • Wallich R, Jahraus O, Stehle T, Thran TTT, Brenner C, Hofmann H, et al (2003) Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease. Eur J Immunol 33: 708–719

    Article  CAS  PubMed  Google Scholar 

  • Casjens S, van Vugt R, Tilly K, Rosa PA, Stevenson B (1997) Homology throughout the multiple 32-kilobase circular plasmids present in Lyme disease spirochetes. J Bacteriol 179: 217–227

    CAS  PubMed  Google Scholar 

  • Kühn S, Zipfel PF (1995) The baculovirus expression vector pBSV-8His directs secretion of histidine-tagged proteins. Gene 162: 225–229

    Article  PubMed  Google Scholar 

  • Prodinger W, Hellwage J, Spruth M, Dierich MP, Zipfel PF (1998) The C-terminus of factor H: monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor H-related proteins. Biochem J 31: 41–47

    Google Scholar 

  • Setubal JC, Reis M, Matsunaga J, Haake DA (2006) Lipoprotein computational prediction in spirochetal genomes. Microbiol 152: 113–121

    Article  CAS  Google Scholar 

  • Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, et al (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390: 580–586

    Article  CAS  PubMed  Google Scholar 

  • Cordes FS, Roversi P, Kraiczy P, Simon MM, Brade V, Jahraus O, et al (2005) A novel fold for the factor H-binding protein BbCRASP-1 of Borrelia burgdorferi. Nat Struct Mol Biol 12: 276–277

    Article  CAS  PubMed  Google Scholar 

  • Kurtenbach K, Sewell H-S, Ogden NH, Randolph SE, Nuttall PA (1998) Serum complement sensitivity as a key factor in Lyme disease ecology. Infect Immun 66: 1248–1251

    CAS  PubMed  Google Scholar 

  • Ojaimi C, Brooks C, Casjens S, Rosa P, Elias A, Barbour A, et al (2003) Profiling of temperature-induced changes in Borrelia burgdorferi gene expression by using whole genome arrays. Infect Immun 71: 1689–1705

    Article  CAS  PubMed  Google Scholar 

  • von Lackum K, Miller JC, Bykowski T, Riley SP, Woodman ME, Brade V, et al (2005) Borrelia burgdorferi regulates expression of complement regulator-acquiring protein 1 during the mammal-tick infection cycle. Infect Immun 73: 7398–7405

    Article  CAS  PubMed  Google Scholar 

  • Brooks CS, Vuppala SR, Jett AM, Akins DR (2006) Identification of Borrelia burgdorferi outer surface proteins. Infect Immun 74: 296–304

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany

    Peter Kraiczy & Volker Brade

  2. Infectious Immunology Group, Institute for Immunology, University of Heidelberg, Heidelberg, Germany

    Evelyn Rossmann & Reinhard Wallich

  3. Max-Planck-Institute for Immunobiology, Freiburg, Germany

    Markus M. Simon

  4. Molecular Immunobiology Group and Department of Infection Biology, Leibniz-Institute for Natural Product Research and Infection Biology, Jena, Germany

    Christine Skerka & Peter F. Zipfel

Authors
  1. Peter Kraiczy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evelyn Rossmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Volker Brade
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Markus M. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christine Skerka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter F. Zipfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Reinhard Wallich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Kraiczy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kraiczy, P., Rossmann, E., Brade, V. et al. Binding of human complement regulators FHL-1 and factor H to CRASP-1 orthologs of Borrelia burgdorferi . Wien Klin Wochenschr 118, 669–676 (2006). https://doi.org/10.1007/s00508-006-0691-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-006-0691-1

Keywords

Search

Navigation