Heterologous Surface Display Reveals Conserved Complement Inhibition and Functional Diversification ofBorrelia burgdorferiElp Proteins

Abstract

AbstractLyme disease is a tick-borne spirochetosis with diverse clinical manifestations. Phenotypic variation amongBorrelia burgdorferistrains correlates with variable manifestations of Lyme disease in humans; this diversity is attributed in part to variation in surface-exposed lipoproteins, which are targets of the human antibody response and contribute to tissue adhesion, immune evasion, and other host interactions. ManyB. burgdorferilipoproteins are encoded as multi-copy gene families including the OspE/F- like leader peptide (Elp) protein family. To characterize Elp allelic variants, we adapted thePseudomonas syringaeice nucleation protein (INP) system to presentB. burgdorferilipoproteins on the surface ofEscherichia coli. We identified interactions with classical complement proteins and mapped binding regions in theE. colisystem. We validated interactions using recombinant proteins andB. burgdorferisurface display. By assessing potential interactions with extracellular matrix components, we identified a novel interaction between Elp proteins and perlecan, a component of mammalian basement membranes, and revealed the bifunctional nature of Elps. Our findings reveal that Elps have undergone functional diversification while maintaining classical complement inhibition mediated by potent and conserved C1s binding and demonstrate thatE. colisurface display offers an efficient, cost-effective, and relatively high throughput approach to characterizeB. burgdorferilipoproteins.