title: 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.
abstract: 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.
authors.affiliation: Infectious Immunology Group, Institute for Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Rossmann
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
authors.forename: Pia
authors.initials: P
authors.lastname: Herzberger
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
authors.forename: Michael
authors.initials: M
authors.lastname: Kirschfink
authors.forename: Markus M
authors.initials: MM
authors.lastname: Simon
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wallich
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001770:Blood Bactericidal Activity / Q000276:immunology; D001798:Blood Proteins / Q000378:metabolism; D001898:Borrelia / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D003001:Cloning, Molecular; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D016384:Consensus Sequence; D003602:Cytotoxicity, Immunologic; D005341:Fibrinolysin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D012061:Relapsing Fever / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D020449:Repetitive Sequences, Amino Acid; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; D008074:Lipoproteins; D037521:Virulence Factors; C521023:complement regulator-acquiring surface protein-1, Borrelia hermsii; C100631:factor H-related protein 1; D017242:Complement Factor H; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin