Ixodes ticks are vectors of several pathogens including Borrelia burgdorferi. Tick saliva contains numerous molecules that facilitate blood feeding without host immune recognition and rejection. We have expressed, purified, and characterized Ixodes scapularis salivary protein 20 (Salp20), a potential inhibitor of the alternative complement pathway that shares homology with the Isac protein family. When analysed by SDS-PAGE and size exclusion chromatography, Salp20 was approximately 48 kDa, more than double its predicted mass, primarily due N- and O-linked glycosylations. Recombinant Salp20 inhibited the alternative complement pathway by dissociating the C3 convertase, and partially protected a serum sensitive species of Borrelia from lysis by normal human serum. We propose that Salp20 facilitates tick feeding and possibly protects tick-borne pathogens from complement components.

Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes scapularis anti-complement protein-like family of tick salivary proteins that inhibit the alternative complement pathway. In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, stabilizing the molecule. Salp20 directly bound to and displaced properdin from the C3 convertase. Displacement of properdin accelerated the decay of the C3 convertase, leading to inhibition of the alternative pathway. S20NS is distinct from known decay accelerating factors, such as decay accelerating factor, complement receptor 1, and factor H, which directly interact with either C3b or cleaved factor B.

Spirochetes in the genus Borrelia are responsible for tick-borne relapsing fever and Lyme disease. Borrelia-tick interactions are highly specific as each species of Borrelia is only transmitted by one or a few closely related species of ticks. Borrelia colonize the gut or salivary glands of ticks. Several Borrelia genes required for tick colonization or transmission have been identified. Borrelia genes required for transmission are induced by a pathway controlled by the alternate sigma factors RpoN (?54) and RpoS (?S). A protein in the gut of I. scapularis ticks that functions as a receptor for B. burgdorferi has been identified. In addition, Ixodes tick saliva has proteins that alter host hemostasis and immunity, and some of these salivary proteins directly interact with Borrelia to facilitate transmission and host infection, whereas others appear to assist Borrelia indirectly by suppressing host defense mechanisms. The exciting discoveries on Borrelia-tick interactions are also being translated into novel preventive measures such as transmission blocking vaccines.

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