A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays

• Published in: Communications biology Vol. 6; no. 1; p. 713
• Main Authors: Miyazaki, Yukiko, Vos, Martijn W., Geurten, Fiona J. A., Bigeard, Pierre, Kroeze, Hans, Yoshioka, Shohei, Arisawa, Mitsuhiro, Inaoka, Daniel Ken, Soulard, Valerie, Dechering, Koen J., Franke-Fayard, Blandine, Miyazaki, Shinya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.07.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154/1435; 631/326/417; Animals; Animals, Genetically Modified; Antimalarials - pharmacology; Biological Assay; Biology; Biomedical and Life Sciences; Blood; Drug development; High-throughput screening; Humans; Life cycles; Life Sciences; Liver; Malaria; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-05078-5

Transgenic luciferase-expressing Plasmodium falciparum parasites have been widely used for the evaluation of anti-malarial compounds. Here, to screen for anti-malarial drugs effective against multiple stages of the parasite, we generate a P. falciparum reporter parasite that constitutively expresses NanoLuciferase (NanoLuc) throughout its whole life cycle. The NanoLuc-expressing P. falciparum reporter parasite shows a quantitative NanoLuc signal in the asexual blood, gametocyte, mosquito, and liver stages. We also establish assay systems to evaluate the anti-malarial activity of compounds at the asexual blood, gametocyte, and liver stages, and then determine the 50% inhibitory concentration (IC 50 ) value of several anti-malarial compounds. Through the development of this robust high-throughput screening system, we identify an anti-malarial compound that kills the asexual blood stage parasites. Our study highlights the utility of the NanoLuc reporter line, which may advance anti-malarial drug development through the improved screening of compounds targeting the human malarial parasite at multiple stages. Presentation of a versatile Plasmodium falciparum dual reporter line, expressing both a fluorescent protein and NanoLuc under a constitutive promoter, that can be used to screen for novel anti-malarial drugs effective against multiple stages of the parasite.