Complement Evasion byBorrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

Abstract

The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other 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 sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence 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) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. 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, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

Streptococcus pneumoniaeEvades Complement Attack and Opsonophagocytosis by Expressing thepspCLocus-Encoded Hic Protein That Binds to Short Consensus Repeats 8–11 of Factor H

“…The strains HB565 (encapsulated, Hic-positive), PR218 (unencapsulated, Hic-positive), and FP13 (unencapsulated, Hic-negative) were incubated with radiolabeled fH, SCR1-7, or SCR8 -20 (7,20, and 30 ng/reaction, respectively) and centrifuged through 20% sucrose. As shown in Fig.…”

Immune evasion of Borrelia burgdorferi: mapping of a complement‐inhibitor factor H‐binding site of BbCRASP‐3, a novel member of the Erp protein family

“…It has been suggested that resistance to complement-mediated killing increases virulence of pathogens and also plays an important role for host specificity [7]. The three human pathogenic genospecies of the B. burgdorferi sensu lato complex, B. burgdorferi, B. garinii, and B. afzelii, differ in their susceptibilities to human complement-mediated lysis [8][9][10][11][12][13]. We have recently reported that serum resistance of Borrelia correlates directly with the acquisition of fluid-phase human complement regulators factor H and FHL-1 [14,15].…”

Complement Resistance of Borrelia burgdorferi Correlates with the Expression of BbCRASP-1, a Novel Linear Plasmid-encoded Surface Protein That Interacts with Human Factor H and FHL-1 and Is Unrelated to Erp Proteins

“…Direct activation of complement via the alternative or the mannose-binding lectin pathway results in opsonization and formation of the lytic membrane attack complex leading to killing of the invading microorganisms (10). An increasing number of microorganisms pathogenic to humans, including B. burgdorferi (11)(12)(13), Neisseria gonorrhoeae (14), Neisseria meningitidis (15), Streptococcus pyogenes (16 -19), and Streptococcus pneumoniae (20), resist complementmediated killing by coating their surfaces with host-derived fluid phase negative complement regulators of the alternative pathway, factor H, and/or factor H-like protein 1 (FHL-1). 1 Factor H and FHL-1 belong to a protein family that is structurally composed of individually folded protein domains, termed short consensus repeats (SCRs), or complement control protein modules (21,22).…”