The Pathogen Box

element-invisible
Catalysing neglected disease drug discovery

Screening the Pathogen Box against Plasmodium sexual stages using a new nanoluciferase based transgenic line of P. berghei identifies transmission-blocking compounds

04 September 2018

Calit J, Dobrescu I, Gaitán XA, Borges MH, Ramos MS, Eastman RT, Bargieri DY

Antimicrobial Agents and Chemotherapy

doi: 10.1128/AAC.01053-18

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 (SMFA), a labor intensive assay. Here we demonstrate 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 (MMV) using the newmodel 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.

View the full article on the Antimicrobial Agents and Chemotherapy website.