Investigations into the Metabolic Requirements for Lipoic Acid and Lipid Species During the Life Cycle of the Malarial Parasite Plasmodium Berghei

Plasmodium, like many other pathogenic organisms, relies on a balance of synthesis and scavenging of lipid species for replication. How the parasite creates this balance is particularly important to successfully intervene in transmission of the disease and to generate new chemotherapies to cure infections. This study focuses on two specific aspects in the field of lipid biology of Plasmodium parasites and their hosts. Lipoic acid is a short eight-carbon chain that serves a number of different functions with the cell. By disrupting a key enzyme in the lipoic acid synthesis pathway in the rodent species of malaria, Plasmodium berghei, we sought to investigate its role during the parasite life-cycle. Deletion of the lipoyl-octanoyl transferase enzyme, LipB in P. berghei parasites demonstrate a liver-stage specific need for this metabolic pathway. In order to explore the impact of the fatty acid and triglyceride content on the pathogenesis of Plasmodium parasites, this study tests two methods to reduce lipid content in vivo and test the propagation of P. berghei parasite in these environments. Results from this study set forth new avenues of research with implications for the development of novel antimalarials and vaccine candidates.