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  • Luciferase-Based, High-Throughput Assay for Screening and Profiling Transmission-Blocking Compounds against Plasmodium falciparum Gametocytes

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    AveryPUB2475.pdf (1.498Mb)
    Author(s)
    Lucantoni, Leonardo
    Fidock, David A
    Avery, Vicky M
    Griffith University Author(s)
    Avery, Vicky M.
    Lucantoni, Leonardo
    Year published
    2016
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    Abstract
    The discovery of new antimalarial drugs able to target both the asexual and gametocyte stages of Plasmodium falciparum is critical to the success of the malaria eradication campaign. We have developed and validated a robust, rapid, and cost-effective high-throughput reporter gene assay to identify compounds active against late-stage (stage IV and V) gametocytes. The assay, which is suitable for testing compound activity at incubation times up to 72 h, demonstrates excellent quality and reproducibility, with average Z′ values of 0.85 ± 0.01. We used the assay to screen more than 10,000 compounds from three chemically diverse ...
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    The discovery of new antimalarial drugs able to target both the asexual and gametocyte stages of Plasmodium falciparum is critical to the success of the malaria eradication campaign. We have developed and validated a robust, rapid, and cost-effective high-throughput reporter gene assay to identify compounds active against late-stage (stage IV and V) gametocytes. The assay, which is suitable for testing compound activity at incubation times up to 72 h, demonstrates excellent quality and reproducibility, with average Z′ values of 0.85 ± 0.01. We used the assay to screen more than 10,000 compounds from three chemically diverse libraries. The screening outcomes highlighted the opportunity to use collections of compounds with known activity against the asexual stages of the parasites as a starting point for gametocytocidal activity detection in order to maximize the chances of identifying gametocytocidal compounds. This assay extends the capabilities of our previously reported luciferase assay, which tested compounds against early-stage gametocytes, and opens possibilities to profile the activities of gametocytocidal compounds over the entire course of gametocytogenesis.
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    Journal Title
    Antimicrobial Agents and Chemotherapy
    Volume
    60
    Issue
    4
    DOI
    https://doi.org/10.1128/AAC.01949-15
    Copyright Statement
    © 2016 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Medical Microbiology not elsewhere classified
    Microbiology
    Medical Microbiology
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/142115
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    • Journal articles

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