PDF(Pubmed)
Abstract：
Malaria parasites must acquire all necessary nutrients from the vertebrate and mosquito hosts to successfully complete their life cycle. Failure to acquire these nutrients can limit or even block parasite development and presents a novel target for malaria control. One such essential nutrient is pantothenate, also known as vitamin B5, which the parasite cannot synthesize de novo and is required for the synthesis of coenzyme A (CoA) in the parasite. This review examines pantothenate and the CoA biosynthesis pathway in the human-mosquito-malaria parasite triad and explores possible approaches to leverage the CoA biosynthesis pathway to limit malaria parasite development in both human and mosquito hosts. This includes a discussion of sources for pantothenate for the mosquito, human, and parasite, examining the diverse strategies used by the parasite to acquire substrates for CoA synthesis across life stages and host resource pools and a discussion of drugs and alternative approaches being studied to disrupt CoA biosynthesis in the parasite. The latter includes antimalarial pantothenate analogs, known as pantothenamides, that have been developed to target this pathway during the human erythrocytic stages. In addition to these parasite-targeted drugs, we review studies of mosquito-targeted allosteric enzymatic regulators known as pantazines as an approach to limit pantothenate availability in the mosquito and subsequently deprive the parasite of this essential nutrient.
摘要：
疟疾寄生虫必须从脊椎动物和蚊子宿主获得所有必需的营养才能成功完成其生命周期。未能获得这些营养素会限制甚至阻止寄生虫的发育，并成为疟疾控制的新目标。一种这样的必需营养素是泛酸，也被称为维生素B5,其寄生虫不能从头合成并且是寄生虫中辅酶A(CoA)的合成所必需的。这篇综述研究了人-蚊子-疟疾寄生虫三联体中的泛酸盐和CoA生物合成途径，并探讨了利用CoA生物合成途径限制人和蚊子宿主中疟疾寄生虫发育的可能方法。这包括讨论蚊子泛酸的来源，人类,和寄生虫，研究了寄生虫在生命阶段和宿主资源库中获得CoA合成底物的多种策略，并讨论了正在研究的破坏寄生虫中CoA生物合成的药物和替代方法。后者包括抗疟疾泛酸类似物，被称为泛酸酰胺，在人类红细胞阶段已经开发出针对该途径的方法。除了这些针对寄生虫的药物，我们回顾了以蚊子为目标的变构酶调节剂的研究，该调节剂被称为pantazine，作为一种限制泛酸在蚊子中的可利用性的方法，随后剥夺了寄生虫的这种必需营养素。
