| Full text | |
| Author(s): |
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]
Total Authors: 7
|
| Affiliation: | [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
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Antimicrobial Agents and Chemotherapy; v. 62, n. 11 NOV 2018. |
| Web of Science Citations: | 4 |
| Abstract | |
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) | |
| FAPESP's process: | 14/23083-1 - Plasmodium vivax vaccine development and antigen discovery using P. berghei malaria models. |
| Grantee: | Irina Dobrescu |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 13/13119-6 - Cell biology and molecular genetics of hemoparasites |
| Grantee: | Daniel Youssef Bargieri |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 16/16649-4 - Expression, purification and immunological analysis of p. berghei MTRAP |
| Grantee: | Xiomara Alexandra Gaitán |
| Support Opportunities: | Scholarships in Brazil - Master |