Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, United States.
Front Immunol. 2023 Jan 31;14:1056469. doi: 10.3389/fimmu.2023.1056469. eCollection 2023.
Schistosomes are long-lived parasitic worms that infect >200 million people globally. The intravascular life stages are known to display acetylcholinesterase (AChE) activity internally as well as, somewhat surprisingly, on external tegumental membranes. Originally it was hypothesized that a single gene (SmAChE1 in ) encoded both forms of the enzyme. Here, we demonstrate that a second gene, designated " tegumental acetylcholinesterase, SmTAChE", is responsible for surface, non-neuronal AChE activity. The SmTAChE protein is GPI-anchored and contains all essential amino acids necessary for function. AChE surface activity is significantly diminished following SmTAChE gene suppression using RNAi, but not following SmAChE1 gene suppression. Suppressing SmTAChE significantly impairs the ability of parasites to establish infection in mice, showing that SmTAChE performs an essential function for the worms . Living and parasites also display strong surface AChE activity, and we have cloned SmTAChE homologs from these two species. This work helps to clarify longstanding confusion regarding schistosome AChEs and paves the way for novel therapeutics for schistosomiasis.
血吸虫是一种寿命长的寄生蠕虫，感染全球超过 2 亿人。已知血管内生活阶段在内部以及相当出人意料地在外部表皮膜上显示乙酰胆碱酯酶 (AChE) 活性。最初假设一个单一基因（ 中的 SmAChE1 ）编码两种形式的酶。在这里，我们证明第二个基因，称为“表皮乙酰胆碱酯酶，SmTAChE”，负责表面非神经元 AChE 活性。SmTAChE 蛋白是 GPI 锚定的，包含功能所必需的所有必需氨基酸。使用 RNAi 抑制 SmTAChE 基因后，AChE 表面活性显着降低，但抑制 SmAChE1 基因后则不然。抑制 SmTAChE 显著削弱了寄生虫在小鼠中建立感染的能力，表明 SmTAChE 对蠕虫的功能至关重要。活的 和 寄生虫也显示出强烈的表面 AChE 活性，我们已经从这两个物种中克隆了 SmTAChE 同源物。这项工作有助于澄清长期以来关于血吸虫乙酰胆碱酯酶的混淆，并为血吸虫病的新疗法铺平了道路。
