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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaotian Tang ◽  
Yongguo Cao ◽  
Gunjan Arora ◽  
Jesse Hwang ◽  
Andaleeb Sajid ◽  
...  

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.

2021 ◽  
Author(s):  
Xiaotian Tang ◽  
yongguo cao ◽  
Gunjan Arora ◽  
Jesse Hwang ◽  
Andaleeb Sajid ◽  
...  

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.


2010 ◽  
Vol 6 (11) ◽  
pp. e1001205 ◽  
Author(s):  
Jianfeng Dai ◽  
Sukanya Narasimhan ◽  
Lili Zhang ◽  
Lei Liu ◽  
Penghua Wang ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Karie E. Robertson ◽  
Chloe D. Truong ◽  
Felicia M. Craciunescu ◽  
Jay-How Yang ◽  
Po-Lin Chiu ◽  
...  

AbstractMembrane-embedded proteins are critical to the establishment, survival and persistence in the host of the Lyme disease bacterium Borrelia burgdorferi (Bb), but to date, there are no solved structures of transmembrane proteins representing these attractive therapeutic targets. All available structures from the genus Borrelia represent proteins expressed without a membrane-targeting signal peptide, thus avoiding conserved pathways that modify, fold and assemble membrane protein complexes. Towards elucidating structure and function of these critical proteins, we directed translocation of eleven expression-optimized Bb virulence factors, including the signal sequence, to the Escherichia coli membrane, of which five, BBA57, HtrA, BB0238, BB0323, and DipA, were expressed with C-terminal His-tags. P66 was also expressed using the PelB signal sequence fused to maltose binding protein. Membrane-associated BBA57 lipoprotein was solubilized by non-ionic and zwitterionic detergents. We show BBA57 translocation to the outer membrane, purification at a level sufficient for structural studies, and evidence for an α-helical multimer. Previous studies showed multiple critical roles of BBA57 in transmission, joint arthritis, carditis, weakening immune responses, and regulating other Bb outer surface proteins. In describing the first purification of membrane-translocated BBA57, this work will support subsequent studies that reveal the precise mechanisms of this important Lyme disease virulence factor.


BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Sherwood R. Casjens ◽  
Eddie B. Gilcrease ◽  
Marija Vujadinovic ◽  
Emmanuel F. Mongodin ◽  
Benjamin J. Luft ◽  
...  

2018 ◽  
Vol 55 (3) ◽  
pp. 501-514 ◽  
Author(s):  
Ellen Y Stromdahl ◽  
Robyn M Nadolny ◽  
Graham J Hickling ◽  
Sarah A Hamer ◽  
Nicholas H Ogden ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document