Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
PLoS Negl Trop Dis. 2012;6(6):e1668. doi: 10.1371/journal.pntd.0001668. Epub 2012 Jun 5.
Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly.
等温微量热法是一种用于测量物理、化学或生物过程热流的成熟工具。活细胞的代谢会产生热量，如果存在足够数量的细胞，则可以通过这种方法评估它们的产热情况。在这项研究中，我们研究了两种医学上重要的原生动物，即罗得西亚锥虫和恶性疟原虫的热流。这些病原体的热流信号使我们能够实时监测寄生虫的生长情况，因为这些信号与活细胞的数量相关。为了展示微量热法在测量药物对致病生物的作用方面的潜力，我们用三种抗锥虫药物，即美拉胂醇、苏拉明和喷他脒，以及三种抗疟药物，即氯喹、青蒿素和双氢青蒿素，每种药物在两个浓度下，对相应的寄生虫进行了测试。通过实时测量，与未处理的对照样品相比，热流的减少立即观察到抑制作用。药物作用的开始、抑制程度和寄生虫培养物的死亡时间可以方便地在几天内进行监测。微量热法是用于发现人类非洲锥虫病和疟疾等原生动物疾病药物的重要工具之一。该方法可能适用于其他原生动物寄生虫，特别是那些在细胞外生长的寄生虫。
