Phospholipases of malaria parasite: Role in pathogenesis and potential as drug targets

Malaria remains a major infectious disease burden, causing more than 600,000 deaths every year globally. The malaria parasite of the genus Plasmodium has gained resistance against most of the leading antimalarial drugs, making them ineffective. To combat the issue of drug resistance, constant efforts are required to design new series of antimalarials. A critical approach to drug discovery is to identify unique and essential metabolic pathways in the parasite and design specific inhibitors for key enzymes of these pathways. The lipid metabolic pathway of the parasite is a promising avenue for developing novel therapeutics, as it encompasses several steps/reactions distinctly different from host counterparts, and several enzymes of lipid metabolic pathways have been found to be essential for malaria parasite pathogenesis. Phospholipases are lipid hydrolyzing enzymes that play a central role in lipid metabolism and homeostasis in Plasmodium. In this chapter, we review the lipid metabolism and homeostasis in the malaria parasite, specifically focusing on phospholipases, their functional roles in pathogenesis, and their potential as novel drug targets for designing new therapeutic interventions against evolving malaria parasites.