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  Dual Binding Specificity of a Borrelia hermsii-Associated Complement Regulator-Acquiring Surface Protein for Factor H and Plasminogen Discloses a Putative Virulence Factor of Relapsing Fever Spirochetes

Rossmann, E., Kraiczy, P., Herzberger, P., Skerka, C., Kirschfink, M., Simon, M. M., et al. (2007). Dual Binding Specificity of a Borrelia hermsii-Associated Complement Regulator-Acquiring Surface Protein for Factor H and Plasminogen Discloses a Putative Virulence Factor of Relapsing Fever Spirochetes. Journal of Immunology, 178, 7292-7301.

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 Urheber:
Rossmann, Evelyn, Autor
Kraiczy, Peter, Autor
Herzberger, Pia, Autor
Skerka, Christine, Autor
Kirschfink, Michael, Autor
Simon, Markus M.1, Autor           
Zipfel, Peter F., Autor
Wallich, Reinhard, Autor
Affiliations:
1Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243654              

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 Zusammenfassung: Tick-borne relapsing fever in North America is primarily caused by the spirochete Borrelia hermsii. The pathogen employs multiple strategies, including the acquisition of complement regulators and antigenic variation, to escape innate and humoral immunity. In this study we identified in B. hermsii a novel member of the complement regulator-acquiring surface protein (CRASP) family, designated BhCRASP-1, that binds the complement regulators factor H (FH) and FH-related protein 1 (FHR-1) but not FH-like protein 1 (FHL-1). BhCRASP-1 specifically interacts with the short consensus repeat 20 of FH, thereby maintaining FH-associated cofactor activity for factor I-mediated C3b inactivation. Furthermore, ectopic expression of BhCRASP- 1 converted the serum-sensitive Borrelia burgdorferi B313 strain into an intermediate complement-resistant strain. Finally, we report for the first time that BhCRASP-1 binds plasminogen/plasmin in addition to FH via, however, distinct nonoverlapping domains. The fact that surface-bound plasmin retains its proteolytic activity suggest that the dual binding specificity of BhCRASP-1 for FH and plasminogen/plasmin contributes to both the dissemination/invasion of B. hermsii and its resistance to innate immunity.

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Sprache(n): eng - English
 Datum: 2007
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 330841
 Art des Abschluß: -

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Titel: Journal of Immunology
  Alternativer Titel : J. Immunol.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 178 Artikelnummer: - Start- / Endseite: 7292 - 7301 Identifikator: -