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Functional characterization of BbCRASP‐2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL‐1
Author(s) -
Hartmann Kristina,
Corvey Carsten,
Skerka Christine,
Kirschfink Michael,
Karas Michael,
Brade Volker,
Miller Jennifer C.,
Stevenson Brian,
Wallich Reinhard,
Zipfel Peter F.,
Kraiczy Peter
Publication year - 2006
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2006.05318.x
Subject(s) - borrelia burgdorferi , factor h , biology , c3 convertase , borrelia , complement system , complement factor b , complement factor i , alternative complement pathway , decay accelerating factor , plasma protein binding , virulence factor , microbiology and biotechnology , genetics , gene , antibody , virulence
Summary Borrelia burgdorferi , the aetiological agent of Lyme disease, employs sophisticated means to survive in diverse mammalian hosts. Recent studies demonstrated that acquisition of complement regulators factor H and factor H‐like protein‐1 (FHL‐1) allows spirochetes to resist complement‐mediated killing. Serum‐resistant B. burgdorferi express up to five distinct complement regulator‐acquiring surface proteins (CRASPs) that bind factor H and/or FHL‐1. In this study we have identified and characterized one of those B. burgdorferi proteins, named BbCRASP‐2. BbCRASP‐2 is distinct from the four previously identified factor H/FHL‐1‐binding CRASPs of B. burgdorferi strains. The single copy of the gene encoding BbCRASP‐2, cspZ , is located on the linear plasmid lp28‐3. BbCRASP‐2 is highly divergent from the factor H/FHL‐1‐binding protein BbCRASP‐1 and from members of the factor H‐binding Erp (OspE/F‐related) protein family. Peptide mapping analysis revealed that the factor H/FHL‐1 binding site is discontinuous and it was found that C‐terminal truncations abrogate factor H and FHL‐1 binding. The predominant BbCRASP‐2 binding site of both host complement regulators was mapped to the short consensus repeat 7 (SCR 7). Factor H and FHL‐1 bound to BbCRASP‐2 maintain cofactor activity for factor I‐mediated C3b inactivation and accelerate the decay of the C3 convertase. Expression of BbCRASP‐2 in serum‐sensitive B. burgdorferi mutant B313 increased resistance to complement‐mediated lysis. The characterization of BbCRASP‐2 now provides a complete picture of the three diverse complement regulator‐binding protein families of B. burgdorferi yielding new insights into the pathogenesis of Lyme disease.