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

• Verfasst von: Kraiczy, Peter [VerfasserIn]
• Verfasst von: Hellwage, Jens [VerfasserIn]
• Verfasst von: Skerka, Christine [VerfasserIn]
• Verfasst von: Becker, Heiko [VerfasserIn]
• Verfasst von: Kirschfink, Michael [VerfasserIn]
• Verfasst von: Simon, Markus M. [VerfasserIn]
• Verfasst von: Brade, Volker [VerfasserIn]
• Verfasst von: Zipfel, Peter F. [VerfasserIn]
• Verfasst von: Wallich, Reinhard [VerfasserIn]
• Titel: 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
• Verf.angabe: Peter Kraiczy, Jens Hellwage, Christine Skerka, Heiko Becker, Michael Kirschfink, Markus M. Simon, Volker Brade, Peter F. Zipfel, Reinhard Wallich
• Jahr: 2004
• Umfang: 8 S.
• Fussnoten: Gesehen am 22.02.2021
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2004
• Band/Heft Quelle: 279(2004), 4, Seite 2421-2429
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M308343200
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Amino Acid Sequence
• Sach-SW: Bacterial Outer Membrane Proteins
• Sach-SW: Bacterial Proteins
• Sach-SW: Base Sequence
• Sach-SW: Blood Proteins
• Sach-SW: Borrelia burgdorferi
• Sach-SW: Complement Activation
• Sach-SW: Complement C3b Inactivator Proteins
• Sach-SW: Complement Factor H
• Sach-SW: Humans
• Sach-SW: Lyme Disease
• Sach-SW: Membrane Proteins
• Sach-SW: Molecular Sequence Data
• Sach-SW: Mutation
• Sach-SW: Protein Binding
• K10plus-PPN: 1749100932

Abstract

The etiologic agent of Lyme disease, Borrelia burgdorferi, is capable of circumventing the immune defense of a variety of potential vertebrate hosts. Previous work has shown that interaction of host-derived complement regulators, factor H and factor H-like protein 1 (FHL-1), with up to five complement regulator-acquiring surface proteins (CRASPs) expressed by resistant B. burgdorferi sensu lato isolates conferred complement resistance. In addition expression of CRASP-1 is directly correlated with complement resistance of Borrelia species. This work describes the functional characterization of BbCRASP-1 as the dominant factor H and FHL-1-binding protein of B. burgdorferi. The corresponding gene, zs7.a68, is located on the linear plasmid lp54 and is different from factor H-binding Erp proteins that are encoded by genes localized on circular plasmids (cp32). Deletion mutants of BbCRASP-1 were generated, and a high affinity binding site for factor H and FHL-1 was mapped to the C terminus of BbCRASP-1. Similarly, the predominant binding site of factor H and FHL-1 was localized to the short consensus repeat 7. Factor H and FHL-1 maintain their cofactor activity for factor I-mediated C3b inactivation when bound to BbCRASP-1, and factor H is up to 6-fold more efficient in mediating C3b conversion than FHL-1. In conclusion, BbCRASP-1 (i). binds the host complement regulators factor H and FHL-1 with high affinity, (ii). is the key molecule of the complement resistance of spirochetes, and (iii). is distinct from the Erp protein family. Thus, BbCRASP-1 most likely contributes to persistence of B. burgdorferi and to pathogenesis of Lyme disease.