Schistosome parasites kill 250,000 people every year. Treatment of schistosomiasis relies on the drug praziquantel. Unfortunately, a scarcity of molecular tools has hindered the discovery of new drug targets. Here, we describe a large-scale RNA interference (RNAi) screen in adult Schistosoma mansoni that examined the function of 2216 genes. We identified 261 genes with phenotypes affecting neuromuscular function, tissue integrity, stem cell maintenance, and parasite survival. Leveraging these data, we prioritized compounds with activity against the parasites and uncovered a pair of protein kinases (TAO and STK25) that cooperate to maintain muscle-specific messenger RNA transcription. Loss of either of these kinases results in paralysis and worm death in a mammalian host. These studies may help expedite therapeutic development and invigorate studies of these neglected parasites.

血吸虫寄生虫每年导致 25 万人死亡。血吸虫病的治疗依赖于药物吡喹酮。不幸的是，分子工具的缺乏阻碍了新药物靶点的发现。在这里，我们描述了对成年曼氏血吸虫进行的大规模 RNA 干扰 (RNAi) 筛查，检查了 2216 个基因的功能。我们鉴定了 261 个基因，其表型影响神经肌肉功能、组织完整性、干细胞维持和寄生虫存活。利用这些数据，我们优先考虑具有抗寄生虫活性的化合物，并发现了一对协同维持肌肉特异性信使 RNA 转录的蛋白激酶（TAO 和 STK25）。丢失这些激酶中的任何一个都会导致哺乳动物宿主瘫痪和蠕虫死亡。这些研究可能有助于加快治疗方法的开发并激发对这些被忽视的寄生虫的研究。