ArticleScientific reports2015
A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 73 citations in OpenAlex.
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- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
- Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Let it glow: genetically encoded fluorescent reporters in Plasmodium.Malaria journal · 2024Review
- A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays.Communications biology · 2023Article
- Assessment of the drugability of initial malaria infection through miniaturized sporozoite assays and high-throughput screening.Communications biology · 2023Article
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- Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.NPJ vaccines · 2022Article
- In vitro models for human malaria: targeting the liver stage.Trends in parasitology · 2022Review
- Gametocyte-specific and all-blood-stage transmission-blocking chemotypes discovered from high throughput screening on Plasmodium falciparum gametocytes.Communications biology · 2022Article
- Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.Nature communications · 2022Article
- The Nitrobenzoxadiazole Derivative NBDHEX Behaves asPharmaceuticals (Basel, Switzerland) · 2022Article
- Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.Frontiers in cellular and infection microbiology · 2022Review
- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- Streamlined and Robust Stage-Specific Profiling of Gametocytocidal Compounds AgainstFrontiers in cellular and infection microbiology · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (>80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual in vitro screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs.
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