Elucidating antimalarial drug targets/mode-of-action by application of system biology technologies

Abstract

Malaria is one of the world's most important tropical diseases, killing more than a million of an estimated 300-500 million infected people per annum. The species responsible for the most fatalities amongst the genus is Plasmodium falsiparum. Eradication efforts are hampered by two major drawbacks-the absence of an effective vaccine coupled with the widespread occurrence of drug-resistant strains to frontline antimalarials and, of late, the emergence of resistance to current antimalarials of choice. In this regard, the researchers chose the polymine metabolic pathway in P. falciparum as a proof of concept project, to validate the pathway as a drug target and elucidate the (MoA) of cyclohexylamine in P. falciparum 3D7. Drug effects were examined through morphological characterisation of the parasite's life cycle, as well as transcriptomic and proteomic analyses.