A chemical susceptibility profile of the Plasmodium falciparum transmission stages by complementary cell-based gametocyte assays

The Journal of Antimicrobial Chemotherapy
Sarah D'AlessandroPietro Alano

Abstract

As most available antimalarial drugs are ineffective against the Plasmodium falciparum transmission stages, new drugs against the parasite's gametocytes are urgently needed to combat malaria globally. The unique biology of gametocytes requires assays that need to be specific, to faithfully monitor anti-gametocyte activity, and to be easy to perform, cheap and scalable to high-throughput screening (HTS). We developed an HTS cell-based assay with P. falciparum gametocytes specifically expressing a potent luciferase. To confirm HTS hit activity for several parasite genotypes, the luciferase assay and the gametocyte lactate dehydrogenase (LDH) assay, usable on any parasite isolate, were compared by screening antimalarial drugs and determining IC50 values of anti-gametocyte hits from the 'Malaria Box' against early- and late-stage gametocytes. Comparison of the two assays, conducted on the early and on late gametocyte stages, revealed an excellent correlation (R(2) > 0.9) for the IC50 values obtained by the respective readouts. Differences in susceptibility to drugs and compounds between the two parasite developmental stages were consistently measured in both assays. This work indicates that the luciferase and gametocyte LDH assays ...Continue Reading

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Citations

May 23, 2016·Trends in Parasitology·Lyn-Marie BirkholtzPietro Alano
Jul 7, 2017·PLoS Pathogens·Robert E Sinden
Apr 5, 2020·Marine Drugs·María Álvarez-BardónRafael Balaña-Fouce
Sep 20, 2018·Nature Communications·Michael J DelvesJake Baum
May 20, 2020·Drug Design, Development and Therapy·Hamisi M MaleboAnnette Habluetzel
Sep 23, 2020·Pharmaceuticals·Phanankosi MoyoLyn-Marié Birkholtz
Jul 22, 2019·Nature Communications·Grazia CamardaGiancarlo A Biagini
Nov 2, 2021·Antimicrobial Agents and Chemotherapy·Silvia ParapiniAnna Olivieri

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