An Image-Based Drug Susceptibility Assay Targeting the Placental Sequestration of Plasmodium falciparum-Infected Erythrocytes

被引:1
|
作者
Ku, Min-Je [1 ]
Dossin, Fernando de M. [1 ]
Hansen, Michael A. E. [2 ]
Genovesio, Auguste [2 ]
Ayong, Lawrence [1 ]
Freitas-Junior, Lucio H. [1 ]
机构
[1] Inst Pasteur Korea, Ctr Neglected Dis Drug Discovery CND3, Songnam, Gyeonggi Do, South Korea
[2] Inst Pasteur Korea, Ctr Core Technol Image Min, Songnam, Gyeonggi Do, South Korea
来源
PLOS ONE | 2012年 / 7卷 / 08期
基金
新加坡国家研究基金会;
关键词
CHONDROITIN-SULFATE-A; CELL-LINE; ADHESION; MALARIA; CYTOADHERENCE; BINDING; PARASITES; RECEPTOR; PROTEIN; CD36;
D O I
10.1371/journal.pone.0041765
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Placental malaria is a significant cause of all malaria-related deaths globally for which no drugs have been developed to specifically disrupt its pathogenesis. To facilitate the discovery of antimalarial drugs targeting the cytoadherence process of Plasmodium-infected erythrocytes in the placenta microvasculature, we have developed an automated image-based assay for high-throughput screening for potent cytoadherence inhibitors in vitro. Parasitized erythrocytes were drug-treated for 24 h and then allowed to adhere on a monolayer of placental BeWo cells prior to red blood cell staining with glycophorin A antibodies. Upon image-acquisition, drug effects were quantified as the proportion of treated parasitized erythrocytes to BeWo cells compared to the binding of untreated iRBCs. We confirmed the reliability of this new assay by comparing the binding ratios of CSA- and CD36-panned parasites on the placental BeWo cells, and by quantifying the effects of chondroitin sulfate A, brefeldin A, and artemisinin on the binding. By simultaneously examining the drug effects on parasite viability, we could discriminate between cytoadherence-specific inhibitors and other schizonticidal compounds. Taken together, our data establish that the developed assay is highly suitable for drug studies targeting placental malaria, and will facilitate the discovery and rapid development of new therapies against malaria.
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页数:7
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