title: 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.
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.
authors: Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany. Kraiczy@em.uni-frankfurt.de
authors: Peter
authors: P
authors: Kraiczy
authors: Jens
authors: J
authors: Hellwage
authors: Christine
authors: C
authors: Skerka
authors: Heiko
authors: H
authors: Becker
authors: Michael
authors: M
authors: Kirschfink
authors: Markus M
authors: MM
authors: Simon
authors: Volker
authors: V
authors: Brade
authors: Peter F
authors: PF
authors: Zipfel
authors: Reinhard
authors: R
authors: Wallich
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D001798:Blood Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000276:immunology / Q000378:metabolism*; D003167:Complement Activation / Q000276:immunology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D008193:Lyme Disease / Q000097:blood* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D017242:Complement Factor H