The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi.
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.
Hellwage
J
J
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsinki, Finland.
Meri
T
T
Heikkilä
T
T
Alitalo
A
A
Panelius
J
J
Lahdenne
P
P
Seppälä
I J
IJ
Meri
S
S
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins; D001665:Binding Sites; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D013696:Temperature
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D008074:Lipoproteins; C084998:OspE protein, Borrelia burgdorferi; D017242:Complement Factor H; D006493:Heparin