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

Autor: Miyazaki Y; Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 852-8523, Nagasaki, Japan. y.miyazaki@nagasaki-u.ac.jp.; Department of Parasitology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. y.miyazaki@nagasaki-u.ac.jp.; Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. y.miyazaki@nagasaki-u.ac.jp., Vos MW; TropIQ Health Sciences, Transistorweg 5, 6534 AT, Nijmegen, The Netherlands., Geurten FJA; Department of Parasitology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands., Bigeard P; Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, F-75013, Paris, France., Kroeze H; Department of Parasitology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands., Yoshioka S; Graduate School of Pharmaceutical Sciences, Osaka University, 565-0871, Osaka, Japan., Arisawa M; Graduate School of Pharmaceutical Sciences, Osaka University, 565-0871, Osaka, Japan., Inaoka DK; Department of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 852-8523, Nagasaki, Japan.; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, 852-8523, Japan.; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan., Soulard V; Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, F-75013, Paris, France., Dechering KJ; TropIQ Health Sciences, Transistorweg 5, 6534 AT, Nijmegen, The Netherlands., Franke-Fayard B; Department of Parasitology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands., Miyazaki S; Department of Parasitology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. smiyazaki@nagasaki-u.ac.jp.; Department of Cellular Architecture Studies, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 852-8523, Nagasaki, Japan. smiyazaki@nagasaki-u.ac.jp.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Jul 12; Vol. 6 (1), pp. 713. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1038/s42003-023-05078-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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