Binding of human factor H-related protein 1 to serum-resistant Borrelia burgdorferi is mediated by borrelial complement regulator-acquiring surface proteins

J Infect Dis. 2007 Jul 1;196(1):124-33. doi: 10.1086/518509. Epub 2007 May 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Blood Proteins / metabolism*
  • Blotting, Western
  • Borrelia burgdorferi / immunology*
  • Complement Activation
  • Complement C3b Inactivator Proteins
  • Complement Factor H / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Protein Binding
  • Spodoptera / cytology
  • Surface Plasmon Resonance

Substances

  • Bacterial Proteins
  • Blood Proteins
  • CFHR1 protein, human
  • Complement C3b Inactivator Proteins
  • Membrane Proteins
  • complement regulator-acquiring surface proteins, Borrelia burgdorferi
  • factor H-related protein 1
  • Complement Factor H