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Heparin Administered to Anopheles in Membrane Feeding Assays Blocks Plasmodium Development in the Mosquito.
Biomolecules ( IF 5.5 ) Pub Date : 2020-08-01 , DOI: 10.3390/biom10081136
Elena Lantero 1, 2 , Jessica Fernandes 3 , Carlos Raúl Aláez-Versón 4 , Joana Gomes 3 , Henrique Silveira 3 , Fatima Nogueira 3 , Xavier Fernàndez-Busquets 1, 2, 5
Affiliation  

Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite’s ookinete–oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 µg/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.

中文翻译:

膜喂食法中按蚊服用肝素可阻断疟原虫在疟疾中的发育。

鉴于对针对疟原虫寄生虫开发的每种药物的耐药性的惊人发展,迫切需要创新的抗疟疾策略。硫酸化的糖胺聚糖肝素已通过膜饲喂测定法与伯氏疟原虫感染的血液一起送入了按蚊蚊子。已经通过在解剖的昆虫中肠中对卵囊计数来体内研究了蚊子中的卵囊和卵囊病原体阶段之间的过渡,而流式细胞术则在体外跟踪了卵囊与肝素的卵囊相互作用。肝素通过结合卵磷脂来干扰寄生虫的卵囊-卵囊过渡,但不影响受精。与天然肝素相比,高硫酸化肝素是一种更有效的对卵子发育的阻滞剂,在膜饲喂法中以5 µg / mL的剂量提供给蚊子时,可大大减少每个中肠的卵囊数量。将肝素直接递送到蚊子可能代表了快速实施的一种新的抗疟疾策略,因为它不需要立即进行临床试验。
更新日期:2020-08-01
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