Lipoproteome screening of the Lyme disease agent identifies inhibitors of antibody-mediated complement killing

Significance Spirochetal pathogens encode an abundance of lipoproteins that can provide a critical interface with the host environment.Borrelia burgdorferi , the model species for spirochetal biology, must survive an enzootic life cycle defined by fluctuations between vector (tick) and vertebrate host. WhileB. burgdorferi expresses over 80 surface lipoproteins—many of which likely contribute to host survival—theB. burgdorferi lipoproteome is poorly characterized. Here, we generated a platform to rapidly identify targets ofB. burgdorferi surface lipoproteins and identified two paralogs that confer resistance to antibody-initiated complement killing that may promote survival in immunocompetent hosts. This work expands our understanding of complement evasion mechanisms and points toward a discovery approach for identifying host–pathogen interactions central to spirochete pathogenesis.