Malaria Research Laboratory, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, 1117, Hungary.
Department of Physics, BME Budapest University of Technology and Economics, Budapest, 1111, Hungary.
Sci Rep. 2020 Aug 20;10(1):14025. doi: 10.1038/s41598-020-70860-y.
Emergence of resistant Plasmodium species makes drug efficacy testing a crucial part of malaria control. Here we describe a novel assay for sensitive, fast and simple drug screening via the magneto-optical detection of hemozoin, a natural biomarker formed during the hemoglobin metabolism of Plasmodium species. By quantifying hemozoin production over the intraerythrocytic cycle, we reveal that hemozoin formation is already initiated by ~ 6-12 h old ring-stage parasites. We demonstrate that the new assay is capable of drug efficacy testing with incubation times as short as 6-10 h, using synchronized P. falciparum 3D7 cultures incubated with chloroquine, piperaquine and dihydroartemisinin. The determined 50% inhibitory concentrations agree well with values established by standard assays requiring significantly longer testing time. Accordingly, we conclude that magneto-optical hemozoin detection provides a practical approach for the quick assessment of drug effect with short incubation times, which may also facilitate stage-specific assessment of drug inhibitory effects.
耐药疟原虫的出现使得药效测试成为疟疾控制的关键环节。在这里,我们描述了一种通过磁光检测疟原虫血红蛋白代谢过程中形成的天然生物标志物——疟色素,来进行灵敏、快速和简单的药物筛选的新方法。通过定量检测疟色素在红细胞内周期中的产生情况,我们发现疟色素的形成早在 6-12 小时龄的环状期寄生虫中就已经开始了。我们证明,使用同步化的恶性疟原虫 3D7 培养物,并在培养物中加入氯喹、哌喹和双氢青蒿素,新的检测方法能够在 6-10 小时的孵育时间内进行药效测试。确定的 50%抑制浓度与需要更长检测时间的标准检测方法建立的值非常吻合。因此,我们得出结论,磁光检测疟色素为快速评估药物作用提供了一种实用方法,同时也有助于对药物抑制作用进行阶段特异性评估。