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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P-berghei Identifies Transmission-Blocking Compounds

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Autor(es):
Calit, Juliana [1] ; Dobrescu, Irina [1] ; Gaitan, Xiomara A. [1] ; Borges, Miriam H. [1] ; Ramos, Marise S. [1] ; Eastman, Richard T. [2] ; Bargieri, Daniel Y. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil
[2] NIH, Div Preclin Innovat, Natl Ctr Advancing Translat Sci, Rockville, MD - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Antimicrobial Agents and Chemotherapy; v. 62, n. 11 NOV 2018.
Citações Web of Science: 4
Resumo

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. (AU)

Processo FAPESP: 14/23083-1 - Desenvolvimento de vacinas para Plasmodium vivax e descoberta de novos antígenos usando o modelo P. berghei
Beneficiário:Irina Dobrescu
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/13119-6 - Biologia celular e genética molecular de hemoparasitas
Beneficiário:Daniel Youssef Bargieri
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 16/16649-4 - Expressão, purificação e análise imunológica da proteína MTRAP de p. berghei
Beneficiário:Xiomara Alexandra Gaitán
Modalidade de apoio: Bolsas no Brasil - Mestrado