Published on Wed Sep 15 2021

The Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector

Tang, X., cao, y., Arora, G., Hwang, J., Sajid, A., Brown, C., Mehta, S., Marin-Lopez, A., Chuang, Y.-M., Wu, M.-J., Ma, H., Pal, U., Narasimhan, S., Fikrig, E.

Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection.

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Abstract

Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin - suggesting activation by alternative pathways. ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection suggesting that ISARL-signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of ISARL significantly reduced the B. burgdorferi burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with B. burgdorferi survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and B. burgdorferi facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete.