A University of South Florida (USF) Center for Global Health & Infectious Diseases Research team has demonstrated a new screening model to classify antimalarial drugs and to identify drug targets for the most lethal strain of malaria, Plasmodium falciparum.
The National Institutes of Health-funded study appeared online November 6 in the journal Scientific Reports.
The malaria parasite is becoming increasingly resistant to the drug artemisinin as the front-line treatment to combat the mosquito-borne disease, even though artemisinin is given as a combination therapy with another antimalarial drug.
The USF research provides a better understanding how antimalarial drugs work, thus adding ammunition in the race to overcome the spread of multidrug-resistant malaria – a public health threat that could potentially undermine the success of global malaria control efforts.
The global health researchers used a collection of malaria parasite mutants that each had altered metabolism linked to defect in a single P. falciparum gene. They then screened 53 drugs and compounds against 71 of theseP. falciparum piggyBac single insertion mutant parasites. Computational analysis of the response patterns linked the different antimalarial drug candidates and metabolic inhibitors to the specific gene defect.
This novel chemogenomic profiling revealed new insights into the drugs’ mechanisms of action and most importantly identified six new genes critically involved P. falciparum’s response to artemisinin, but with increased susceptibility to the drugs tested.