Phospholipid Biosynthesis in Leishmania Parasites

Leishmania parasites are protozoan pathogens responsible for a spectrum of diseases known as leishmaniasis. Transmitted by sand flies, these parasites are endemic in 88 countries causing 1-2 million new cases annually. There is no reliable vaccine and current treatments are plagued with low efficacy, high cost, and strong adverse effects. To discover new drug targets, it is important to understand the molecular mechanism of Leishmania pathogenesis. Our goal is to unearth the role of phospholipid metabolism in Leishmania growth and virulence. This project will study the biosynthesis of phosphatidylcholine (PtC) which is the most abundant phospholipid in Leishmania. We have identified a putative Choline/Ethanolamine Phosphotransferase (C/EPT) gene from the genome of Leishmania major. C/EPT is directly responsible for the production of PtC as well as a related phospholipid------ phosphatidylethanolamine (PtE). Preliminary study suggests that C/EPT is essential in L. major. To further characterize this enzyme, we will employ a negative selection approach based on segregational loss of episomal complementing genes that has proven successful in the analysis of essential genes in Leishmania. Future studies will elucidate the roles of PtC in Leishmania growth and virulence and evaluate C/EPT as a potential drug target.

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