Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 62, Issue 11, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01053-18
Keywords
HTS; Pathogen Box; antimalarial agents; gametes; malaria; transmission
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/13119-6]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [405996/2016-0]
- Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health
- Instituto Serrapilheira [G-1709-16618]
- FAPESP fellowships [2016/16649-4, 2014/23083-1]
- CNPq [870219/1997-9]
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Malaria remains an important parasitic disease with a large morbidity and mortality burden. Plasmodium transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts. Recent efforts to develop high-throughput screening (HTS) methods to identify compounds that inhibit or kill gametocytes, the Plasmodium sexual stage infectious to mosquitoes, have yielded insight into new TB compounds. However, the activities of these compounds against gametes, formed in the first minutes of mosquito infection, are typically not assessed, unless screened in a standard membrane feeding assay, a labor-intensive assay. We demonstrate here the generation of a Plasmodium model for drug screens against gametes and fertilization. The new P. berghei line, named Ookluc, was genetically and pharmacologically validated and scalable for HTS. Screening the Pathogen Box from the Medicines for Malaria Venture using the new model identified promising TB compounds. The use of Ookluc in different libraries of compounds may aid in the identification of transmission-blocking drugs not assessed in screens against asexual stages or gametocytes.
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