The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi

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.

Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi

“…29 Two type of proteins that may be involved in complement resistance in B. burgdorferi have been reported. One of them is OspE/Erp proteins that bind factor H. 30,31 More recently, a CD59-like molecule that inhibits the assembly of MAC was described on the outer membrane of B. burgdorferi. 32 We found deposition of MAC in the heart of IS-NHPs not only on spirochetes but also on the membranes of cardiac myocytes.…”

Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

“…Orthologous genes have been identified in all other Lyme disease spirochete genospecies, although it is not yet clear whether or not the encoded proteins bind factor H and FHL-1 (Rogers and Marconi, 2007, and our unpublished results). BbCRASP-3, -4, and -5 lipoproteins all belong to the Erp paralog family, and their respective genes are named erpP, erpC, and erpA, or, collectively, ospE (Stevenson et al, 1996Casjens et al, 2000;Hellwage et al, 2001;Alitalo et al, 2002Alitalo et al, ,2004Kraiczy et al, 2003Kraiczy et al, ,2004aMetts et al, 2003). erp loci are all located on borrelial prophages which replicate as circular episomes known as cp32s .…”

“…produces several different outer surface proteins collectively termed CRASPs (complement regulator-acquiring surface proteins). These lipoproteins share affinities for the host fluid phase negative regulators of complement factor H and/or FHL-1 (factor H-like protein 1) (Hellwage et al, 2001;Kraiczy et al, 2001Kraiczy et al, , 2003Kraiczy et al, , 2004aKraiczy et al, , 2004bAlitalo et al, 2002Alitalo et al, , 2005Stevenson et al, 2002;McDowell et al, 2003;Hartmann et al, 2006;Kraiczy and Würzner, 2006;Herzberger et al, 2007). Those two host proteins promote breakdown of C3b and inactivation of the alternative pathway C3 convertase (Janeway et al, 1999;Kraiczy and Würzner, 2006).…”

Serum-Resistant Strains of Borrelia burgdorferi Evade Complement-Mediated Killing by Expressing a CD59-Like Complement Inhibitory Molecule

“…These proteins, that function as cofactors of factor I in the degradation of C3b and C4b, interact with several outer membrane proteins including Osp-E, and reduce the number of C3 molecules deposited on the bacterial surface (23). However, the recent demonstration by Breitner-Ruddock et al (16) that the amount of C3 and that of its degradation products deposited on the bacterial surface do not differ in C-susceptible and C-resistant strains of B. burgdorferi suggests that the ability of surface-bound factor H to control C3 activation is not the only mechanism used by these spirochetes to evade C-dependent destruction.…”