Parasitology, Department of Infectious Diseases, University of Heidelberg Medical School, Heidelberg, Germany.
FASEB J. 2010 Dec;24(12):5003-12. doi: 10.1096/fj.10-164814. Epub 2010 Aug 26.
Malaria is transmitted to the host when Plasmodium sporozoites are injected by a mosquito vector. Sporozoites eventually enter hepatocytes, where they differentiate into liver-stage parasites. During the first hours after hepatocyte invasion, the crescent-shaped sporozoites transform into spherical intracellular exoerythrocytic parasites. This process, which precedes genome replication, can be mimicked in vitro in the absence of host cells. Here, we developed an automated method to follow transformation and cell death of sporozoites in vitro. This assay provides a rapid tool to test sporozoite survival and to screen for antiparasitic drugs. We found that extracellular bicarbonate and high temperature trigger transformation, whereas physiological serum albumin concentrations and media lacking bicarbonate delayed sporozoite death. Because bicarbonate also triggers ookinete transformation and exflagellation of gametocytes, we suggest that a common molecular mechanism regulates similar aspects of stage conversion in Plasmodium.
疟疾是由疟原虫孢子虫通过蚊子媒介注射到宿主时传播的。孢子虫最终进入肝细胞，在那里它们分化成肝期寄生虫。在被肝细胞侵入后的最初几个小时内，新月形的孢子虫转变为球形的细胞内外红细胞外寄生虫。在没有宿主细胞的情况下，这个在基因组复制之前发生的过程可以在体外模拟。在这里，我们开发了一种自动方法来跟踪体外孢子虫的转化和细胞死亡。该测定法提供了一种快速的工具来测试孢子虫的存活并筛选抗寄生虫药物。我们发现细胞外碳酸氢盐和高温触发转化，而生理血清白蛋白浓度和缺乏碳酸氢盐的培养基则延迟孢子虫死亡。因为碳酸氢盐还触发动合子转化和配子体的出芽，我们认为一个共同的分子机制调节疟原虫中类似的阶段转换方面。
