title: Bioluminescence Method forIn VitroScreening of Plasmodium Transmission-Blocking Compounds.
abstract: The sporogonic stage of the life cycle ofPlasmodiumspp., the causative agents of malaria, occurs inside the parasite's mosquito vector, where a process of fertilization, meiosis, and mitotic divisions culminates in the generation of large numbers of mammalian-infective sporozoites. Efforts to cultivatePlasmodiummosquito stagesin vitrohave proved challenging and yielded only moderate success. Here, we describe a methodology that simplifies thein vitroscreening of much-needed transmission-blocking (TB) compounds employing a bioluminescence-based method to monitor thein vitrodevelopment of sporogonic stages of the rodent malaria parasitePlasmodium bergheiOur proof-of-principle assessment of thein vitroTB activity of several commonly used antimalarial compounds identified cycloheximide, thiostrepton, and atovaquone as the most active compounds against the parasite's sporogonic stages. The TB activity of these compounds was further confirmed byin vivostudies that validated our newly developedin vitroapproach to TB compound screening.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Azevedo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Marija
authors.initials: M
authors.lastname: Markovic
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Machado
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Blandine
authors.initials: B
authors.lastname: Franke-Fayard
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal antoniomendes@medicina.ulisboa.pt mprudencio@medicina.ulisboa.pt.
authors.forename: António M
authors.initials: AM
authors.lastname: Mendes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal antoniomendes@medicina.ulisboa.pt mprudencio@medicina.ulisboa.pt.
authors.forename: Miguel
authors.identifier: 0000-0003-1746-6029
authors.initials: M
authors.lastname: Prudêncio
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D007303:Insect Vectors / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy / Q000635:transmission*; D010962:Plasmodium berghei / Q000187:drug effects*; D034101:Sporozoites / Q000187:drug effects
chemical_list: D000962:Antimalarials; D029721:Drosophila Proteins
keywords: Plasmodium berghei; in vitro cultures; malaria; mosquito stages; sporogony