Binding of human factor H-related protein 1 to serum-resistant Borrelia burgdorferi is mediated by borrelial complement regulator-acquiring surface proteins.
BACKGROUND
Isolates of Borrelia burgdorferi, the causative agent of Lyme disease, express up to 5 distinct complement regulator-acquiring surface proteins (CRASP-1, -2, -3, -4, and -5).


METHODS
By use of ligand affinity blotting, enzyme-linked immunosorbent assay, surface plasmon resonance, and functional complement assays, we have identified factor H-related protein 1 (FHR-1) as a novel protein that binds to the bacterium via CRASP-3, -4, and -5.


RESULTS
When incubated in serum, serum-resistant Borrelia burgdorferi strain LW2 bind FHR-1, an additional member of the human factor H protein family, and, similarly, 2 mouse FHR proteins bind to the surface. Recombinant FHR-1 binds to 3 borrelial surface proteins (CRASP-3, -4, and -5) but not to CRASP-1 and -2. A comparative analysis of the individual CRASPs revealed common as well as distinct binding profiles for the 3 human regulators. FHR-1 binds to 3 CRASPs, and factor H binds to all 5 CRASPs. In addition, factor H-like protein 1 interacts with CRASP-1 and -2 but with no other borrelial proteins.


CONCLUSIONS
Thus, by expressing multiple surface proteins with different binding properties, the pathogen can attach a unique combination of host complement regulators to its surface. For the pathogen, this type of surface decoration and specific acquisition of different host plasma proteins allows fine-tuning of the host immune attack.
Haupt
Katrin
K
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
Kraiczy
Peter
P
Wallich
Reinhard
R
Brade
Volker
V
Skerka
Christine
C
Zipfel
Peter F
PF
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D025065:Borrelia burgdorferi / Q000276:immunology*; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D018411:Spodoptera / Q000166:cytology; D020349:Surface Plasmon Resonance
D001426:Bacterial Proteins; D001798:Blood Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D008565:Membrane Proteins; C440651:complement regulator-acquiring surface proteins, Borrelia burgdorferi; C100631:factor H-related protein 1; D017242:Complement Factor H