# Ethanolamine phospholipid synthesis in Leishmania

> **NIH NIH R15** · TEXAS TECH UNIVERSITY · 2021 · $460,738

## Abstract

The goal of this application is to determine how Leishmania parasites acquire ethanolamine
phospholipids (EPL), an abundant class of lipids with vital functions in membrane- and non-membrane
processes. This is significant because a better understanding of EPL acquisition will shed new light on the
unique biochemistry of Leishmania parasites and the results may lead to novel drug targets. In many
eukaryotes, EPL are generated through the ethanolamine branch of the Kennedy pathway, the uptake and
remodeling of exogenous lipids, and the interconversion between phosphatidylserine and
phosphatidylethanolamine. During their life cycle, Leishmania parasites alternate between extracellular
promastigotes in sandflies and intracellular amastigotes in mammals. Preliminary studies demonstrate that the
enzyme ethanolamine-phosphate cytidylyltransferase (EPCT) is absolutely essential for the promastigote AND
amastigote stages of Leishmania major. EPCT is required for the de novo synthesis of EPL via the Kennedy
pathway. In contrast, the de novo synthesis of choline phospholipids, which are far more abundant than EPL, is
fully dispensable for L. major amastigotes, the pathogenic form to humans. Based on these and other findings,
the central hypothesis is that while Leishmania amastigotes can acquire most of their lipids through salvage
and remodeling, they must synthesize a specific subset of EPL that cannot be sufficiently scavenged from the
host. Three specific aims will be undertaken concurrently to test this hypothesis and explore the roles of EPL
synthesis in Leishmania. Aim 1 is to determine why EPCT is indispensable for amastigotes. The plan is to
elucidate the lipidome of intracellular amastigotes, identify those amastigote specific EPL, and reveal the types
of host lipids that are selectively salvaged by amastigotes. Aim 2 is to assess the essentiality of EPCT in
Leishmania donovani and Leishmania amazonensis. This is important because different Leishmania species
may have distinct requirements for lipid uptake and synthesis. This aim will determine whether EPCT is a pan-
Leishmania target and identify the types of EPL that are synthesized via EPCT. Aim 3 is to investigate the roles
of phosphatidylserine decarboxylase and phosphatidylserine synthase. These enzymes have never been
studied in Leishmania and their impact on in EPL synthesis, mitochondria functions, and virulence will be
determined. Successful completion of these aims will reveal how Leishmania acquire EPL through different
pathways and elucidate the crucial functions of EPL. The findings may lead to the identification of new drug
targets (e.g. EPCT) or new strategies to block the essential lipid transfer from host to Leishmania. This project
is well within the principle investigator’s area of expertise and its scope is appropriate for a research team
mainly made of undergraduate and graduate students. In summary, this AREA grant is expected to improve
our understanding of Leishmania biolo...

## Key facts

- **NIH application ID:** 10290816
- **Project number:** 1R15AI156746-01A1
- **Recipient organization:** TEXAS TECH UNIVERSITY
- **Principal Investigator:** Kai Zhang
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,738
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10290816

## Citation

> US National Institutes of Health, RePORTER application 10290816, Ethanolamine phospholipid synthesis in Leishmania (1R15AI156746-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10290816. Licensed CC0.

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