Complement evasion by Borrelia burgdorferi: Serum-resistant strains promote C3b inactivation

The most characteristic features of the Lyme disease pathogens, the Borreli a burgdorferi sensu late (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of t ime, despite elevated levels of borrelia-specific antibodies in serum and o ther body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their s ensitivities to normal human serum and abilities to promote factor I-mediat ed C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains wer e found to be serum resistant. When the spirochetes were incubated with rad iolabeled C3b, factor I-mediated degradation of C3b was observed in the pre sence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) str ains or control bacteria (Escherichia coli, Staphylococcus aureus, and Ente rococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors f actor H and factor H-like protein 1 (FHL-1) from growth medium and human se rum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, th e serum-resistant B. burgdorferi s.l. strains can circumvent C attack by bi nding the C inhibitors factor H and FHL-1 to their surfaces and promoting f actor I-mediated C3b degradation.