Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice 37005, Czech Republic.
Open Biol. 2022 Feb;12(2):210244. doi: 10.1098/rsob.210244. Epub 2022 Feb 16.
It has been demonstrated that impairing protein synthesis using drugs targeted against tRNA amino acid synthetases presents a promising strategy for the treatment of a wide variety of parasitic diseases, including malaria and toxoplasmosis. This is the first study evaluating tRNA synthetases as potential drug targets in ticks. RNAi knock-down of all tested tRNA synthetases had a strong deleterious phenotype on feeding. Our data indicate that tRNA synthetases represent attractive, anti-tick targets warranting the design of selective inhibitors. Further, we tested whether these severely impaired ticks were capable of transmitting spirochaetes. Interestingly, biologically handicapped nymphs transmitted in a manner quantitatively sufficient to develop a systemic infection in mice. These data suggest that initial blood-feeding, despite the incapability of ticks to fully feed and salivate, is sufficient for activating from a dormant to an infectious mode, enabling transmission and dissemination in host tissues.
已经证明,使用针对 tRNA 氨基酸合成酶的药物来抑制蛋白质合成,是治疗包括疟疾和弓形体病在内的多种寄生虫病的一种很有前途的策略。这是第一项评估 tRNA 合成酶作为蜱虫潜在药物靶点的研究。所有测试的 tRNA 合成酶的 RNAi 敲低对 摄食都有很强的有害表型。我们的数据表明,tRNA 合成酶是有吸引力的抗蜱虫靶标,值得设计选择性抑制剂。此外,我们还测试了这些严重受损的蜱虫是否能够传播 螺旋体。有趣的是,生物功能障碍的 若虫以足够定量的方式传播 ,足以在小鼠中引发全身性感染。这些数据表明,尽管蜱虫不能完全进食和分泌唾液,但最初的血液摄入足以使 从休眠状态激活到感染状态,从而能够在宿主组织中传播和扩散。