ErpY-like Lipoprotein of Leptospira Outsmarts Host Complement Regulation by Acquiring Complement Regulators, Activating Alternative Pathways, and Intervening in the Membrane Attack Complex

The survival of pathogenic Leptospira in the host depends on its proficiency to circumvent the immune response. These pathogens evade the complement system in serum by enticing and amassing the serum complement regulators onto their surface. ErpY-like lipoprotein, a surface-exposed protein of Leptospira spp., is conserved in the pathogenic Leptospira serovars. The recombinant form of this protein interacts with multiple extracellular matrix (ECM) components and serum proteins such as soluble complement regulators factor H (FH) and factor I (FI). Here, we document that the supplementation of rErpY-like protein (10 mu g/mL) in human serum inhibits complement-mediated bacterial cell lysis and augments the viability of Escherichia coli and saprophytic Leptospira biflexa by more than two-fold. Complement regulators FH and FI, when bound to rErpY-like protein, preserve their respective cofactor and protease activity and cleave the complement component C3b. The supplementation of rErpY-like protein (40 mu g/mL) in serum ensued in an similar to 90% reduction of membrane attack complex (C5b-9/MAC) deposition through the alternative pathway (AP) of complement activation. However, rErpY-like protein could moderately reduce (similar to 16%) MAC deposition in serum through the classical pathway (CP). In addition, the rErpY-like protein solely initiated the AP, suggesting its role in the rapid consumption and depletion of the complement components. Blocking the pathogenic Leptospira interrogans surface with anti-rErpY-like antibodies resulted in an increase in MAC formation on the bacterial surface, indicating a specific role of the ErpY-like lipoprotein in complement-mediated immune evasion. This study underscores the role of the ErpY-like lipoprotein of Leptospira in complement evasion.