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The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi
J Hellwage1, T Meri, T Heikkilä
1Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsinki, Finland.
Insights
Borrelia bacteria causing Lyme disease evade immune complement attack by binding human factor H. The outer surface protein OspE is identified as a key binding target for factor H.
Area of Science:
- Microbiology and Immunology
- Bacterial Pathogenesis
- Complement System
Background:
- Lyme borreliosis is caused by Borrelia burgdorferi sensu lato spirochetes.
- Pathogenic Borrelia subspecies exhibit varying susceptibility to complement lysis, a key immune defense mechanism.
- Complement resistance may be mediated by the acquisition of host-derived complement inhibitors.
Purpose of the Study:
- To investigate if Borrelia's complement resistance is due to acquiring factor H (fH) and factor H-like protein 1 (fHLP1).
- To identify specific Borrelia surface proteins that bind fH.
- To determine the binding site of fH on identified Borrelia ligands.
Main Methods:
- Exposure of Borrelia strains to nonimmune human plasma.
- Detection of bound fH/fHLP1 using radiolabeled proteins.
- Surface plasmon resonance (SPR) to identify fH ligands on Borrelia outer surface proteins.
- Analysis of recombinant factor H constructs to map binding sites.
Main Results:
- Serum-resistant Borrelia afzelii and Borrelia burgdorferi sensu stricto bound fH/fHLP1 from plasma.
- Factor H showed strong binding to Borrelia burgdorferi sensu stricto.
- The outer surface lipoprotein OspE was identified as a specific ligand for factor H.
- Factor H binding to OspE was localized to C-terminal short consensus repeat domains 15-20.
Conclusions:
- Borrelia burgdorferi sensu stricto acquires host factor H via its outer surface protein OspE.
- This specific binding interaction likely contributes to the pathogen's resistance to complement-mediated lysis.
- Evasion of complement attack and subsequent phagocytosis may be facilitated by this mechanism, aiding Borrelia survival.
Abstract:
Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.