Immune evasion of Borrelia burgdorferi: mapping of a complement-inhibitor factor H-binding site of BbCRASP-3, a novel member of the Erp protein family.
The causative agents of Lyme disease, Borrelia burgdorferi s.s., B. garinii, and B. afzelii, differ in their susceptibility to complement-mediated lysis. This phenomenon apparently depends on the expression of proteins termed complement regulator-acquiring surface proteins (CRASP) and their binding to the inhibitory plasma proteins factor H and FHL-1. To characterize these bacterial proteins in more detail we have now isolated from a B. burgdorferi expression library a novel factor H-binding protein. In accordance with our previous studies this protein was termed BbCRASP-3 and represents a novel member of the polymorphic Erp (OspE/F-related) protein family. On the basis of protease accessibility assays using intact spirochetes, BbCRASP-3 is identified as a surface-exposed protein and binds the C-terminal short consensus repeats of factor H. Applying deletion mutants of BbCRASP-3, the factor H-binding site was mapped to the nine-amino-acid motif LEVLKKNLK localized at the C-terminal end of BbCRASP-3. Factor H bound to BbCRASP-3 maintains its cofactor activity in factor I-mediated C3b inactivation. Binding of BbCRASP-3 to factor H can be inhibited by heparin, a physiological ligand of the complement regulator factor H. Blocking of factor-H-binding by soluble BbCRASP-3 leads to an increase of complement deposition on intermediate serum-resistant strain ZS7. In conclusion, BbCRASP-3 has been identified as a novel factor H-binding protein on B. burgdorferi which by conferring complement resistance to the pathogen may contribute to its persistence in the mammalian host.
Kraiczy
Peter
P
Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt, Germany. Kraiczy@em.uni-frankfurt.de
Hellwage
Jens
J
Skerka
Christine
C
Kirschfink
Michael
M
Brade
Volker
V
Zipfel
Peter F
PF
Wallich
Reinhard
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D025065:Borrelia burgdorferi / Q000276:immunology*; D017242:Complement Factor H / Q000378:metabolism*; D008969:Molecular Sequence Data; D018411:Spodoptera
D017242:Complement Factor H