Azevedo Raquel, Markovic Marija, Machado Marta, Franke-Fayard Blandine, Mendes António M, Prudêncio Miguel
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.02699-16. Print 2017 Jun.
The sporogonic stage of the life cycle of spp., the causative agents of malaria, occurs inside the parasite's mosquito vector, where a process of fertilization, meiosis, and mitotic divisions culminates in the generation of large numbers of mammalian-infective sporozoites. Efforts to cultivate mosquito stages have proved challenging and yielded only moderate success. Here, we describe a methodology that simplifies the screening of much-needed transmission-blocking (TB) compounds employing a bioluminescence-based method to monitor the development of sporogonic stages of the rodent malaria parasite Our proof-of-principle assessment of the TB activity of several commonly used antimalarial compounds identified cycloheximide, thiostrepton, and atovaquone as the most active compounds against the parasite's sporogonic stages. The TB activity of these compounds was further confirmed by studies that validated our newly developed approach to TB compound screening.
疟原虫是疟疾的病原体,其生命周期的孢子生殖阶段发生在寄生虫的蚊子媒介体内,在那里受精、减数分裂和有丝分裂过程最终产生大量可感染哺乳动物的子孢子。培养蚊子阶段的努力已证明具有挑战性,且仅取得了一定程度的成功。在此,我们描述了一种方法,该方法简化了急需的传播阻断(TB)化合物的筛选,采用基于生物发光的方法来监测啮齿动物疟原虫孢子生殖阶段的发育。我们对几种常用抗疟化合物的TB活性进行的原理验证评估确定,环己酰亚胺、硫链丝菌素和阿托伐醌是针对寄生虫孢子生殖阶段最具活性的化合物。这些化合物的TB活性通过研究进一步得到证实,这些研究验证了我们新开发的TB化合物筛选方法。