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.