Binding of human complement regulators FHL-1 and factor H to CRASP-1 orthologs of Borrelia burgdorferi.
The complement regulator-acquiring surface protein (CRASP)-1 is a member of the paralogous gene family gbb54 and the dominant FHL-1 and factor H binding protein of Borrelia burgdorferi sensu stricto (s.s.). It was shown recently that expression of BbCRASP-1 directly correlates with serum resistance of B. burgdorferi s.s. isolates. In the present study we have elucidated the putative potential of other members of the gbb54 paralogous family, including orthologs ZSA66, ZSA69, ZSA70, ZSA71, ZSA72 and ZSA73 of the European B. burgdorferi s.s. strain ZS7, to bind human FHL-1 and factor H. In spite of their overall similarity in protein sequence, between 47% and 67%, and the fact that the C-terminal region of ZSA69 shows 70% similarity with BbCRASP-1, none of the orthologous proteins was able to bind human FHL-1 and/or factor H. BbCRASP-1 is the only member of the paralogous gene family gbb54 that binds to human complement regulators, supporting the notion that BbCRASP-1 plays a critical role in evasion of complement by B. burgdorferi s.s. and thus may be helpful in the development of novel therapeutic strategies against Lyme borreliosis.
Kraiczy
Peter
P
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany. Kraiczy@em.uni-frankfurt.de
Rossmann
Evelyn
E
Brade
Volker
V
Simon
Markus M
MM
Skerka
Christine
C
Zipfel
Peter F
PF
Wallich
Reinhard
R
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D001782:Blood Donors; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis; D006801:Humans; D007113:Immunity, Innate; D008193:Lyme Disease / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001426:Bacterial Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; D017242:Complement Factor H