Complement factor H binding by different Lyme disease and relapsing fever Borrelia in animals and human

Affinity ligand binding experiments, 2-D electrophoresis, and protein identification and peptide de novo sequencing based on mass spectrometry, revealed novel fH putative binding proteins of Lyme- and relapsing fever Borrelia. An OspA serotype-associated differential human and animal fH binding by B. garinii was also observed, which could be related with the ability of some strains from serotypes 4 and 7 to invade non-nervous system tissues. Also, the variable affinity of binding proteins expressed by different Borrelia to animal fH correlated with their host selectivity.The novel animal and human putative fH binding proteins (FHBPs) in this study underscore the importance of evasion of complement in the pathogenesis of Borrelia infections.Binding of fH on the borrelial cell surface is critical for resistance to complement-mediated killing by inhibiting the formation of the terminal complement complex [1,2]. Human fH binding has been reported and its association with the pathogenic nature of Borrelia species was predicted earlier [1,3,4]. Complement resistant strains (e.g. B. afzelii and B. hermsii) survive successfully in body compartments where complement concentration is high, whereas it is proposed that B. garinii strains do not bind fH on their surface and thus are prone to complement-mediated killing; therefore, they would be able to invade the nervous system where complement concentration is low [5]. However, it has been reported that some OspA serotypes of B. garinii can infect and disseminate through the skin [6], and resist human complement mediated killing [7].The nature of human and animal fH binding ability to Borrelia is complex. To date, the majority of studies have focused on human fHBPs of B. burgdorferi s.s., B. afzelii and B. hermsii, using purified fH or recombinant proteins [3,8-10]. In contrast, here we have analyzed a wider panel of Borrelia species, as well as human and different animal sera as source of native fH. We also present how the res