State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
College of Pharmacy, Xinjiang Medical University, Urumqi, China.
Front Cell Infect Microbiol. 2021 Nov 11;11:747739. doi: 10.3389/fcimb.2021.747739. eCollection 2021.
Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of () cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, the role of GLUT1 in (EgGLUT1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from () and found EgGLUT1-ss was crucial for glucose uptake and viability by the protoscoleces of WZB117, a GLUT1 inhibitor, inhibited glucose uptake by and the viability of the metacestode . In addition, WZB117 showed significant therapeutic activity in -infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts ( < 0.05) as efficiently as the reference drug, albendazole. Our results demonstrate that EgGLUT1-ss is crucial for glucose uptake by the protoscoleces of , and its inhibitor WZB117 has a therapeutic effect on CE.
棘球蚴病(CE)是一种由幼虫感染引起的人畜共患寄生虫病。棘球蚴属()簇。迫切需要确定新的药物靶点并开发针对 CE 的新药候选物。葡萄糖转运蛋白 1(GLUT1)主要负责葡萄糖的跨膜转运,以维持其恒定的细胞可用性,是各种疾病中作为药物靶点的研究热点。然而,GLUT1 在(EgGLUT1)中的作用尚不清楚。在这项研究中,我们从()中克隆了一个保守的 GLUT1 同源基因(命名为 EgGLUT1-ss),并发现 EgGLUT1-ss 对 WZB117 的原头节的葡萄糖摄取和活力至关重要,WZB117 是一种 GLUT1 抑制剂,可抑制 和 metacestode 的葡萄糖摄取和活力。此外,WZB117 在感染的小鼠中表现出显著的治疗活性:10 mg/kg 剂量的 WZB117 可显著减少寄生虫囊肿的数量和重量(<0.05),与参考药物阿苯达唑一样有效。我们的结果表明,EgGLUT1-ss 对原头节的葡萄糖摄取至关重要,其抑制剂 WZB117 对 CE 具有治疗作用。