A male and female gametocyte functional viability assay to identify biologically relevant malaria transmission-blocking drugs

07 Oct 2014

EA. Ruecker, D. K. Mathias, U. Straschil, T. S. Churcher, R. R. Dinglasan, D. Leroy, R. E. Sinden, M. J. Delves

Antimicrobial Agents and Chemotherapy



Malaria elimination will require interventions which prevent parasite transmission from the human host to the mosquito. Experimentally, this is usually determined by the expensive and laborious P. falciparum Standard Membrane Feeding Assay (Pf SMFA) which has limited utility for high throughput drug screening. In response, we developed the P. falciparum dual gamete formation assay (Pf DGFA) which faithfully simulates the initial stages of the Pf SMFA in vitro. It utilizes a dual read-out that individually and simultaneously reports on the functional viability of male and female mature Stage V gametocytes. To validate, we screen the MMV Malaria Box library with the Pf DGFA. Unique to this assay, we find compounds that target male gametocytes only and also compounds with reversible and irreversible activity. Most importantly, we show compound activity in the Pf DGFA accurately predicts activity in Pf SMFAs, which validates and supports its adoption into the transmission-stage screening pipeline.

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