Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum

Sonia Gulati, Eric H. Ekland, Kelly V. Ruggles, Robin B. Chan, Bamini Jayabalasingham, Bowen Zhou, Pierre Yves Mantel, Marcus C.S. Lee, Natasha Spottiswoode, Olivia Coburn-Flynn, Daisy Hjelmqvist, Tilla S. Worgall, Matthias Marti, Gilbert Di Paolo, David A. Fidock (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)

Abstract

During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum sexual and asexual blood stage (ABS) development. Using liquid chromatography-mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum, and 70%-75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts.

Original languageEnglish
Pages (from-to)371-381
Number of pages11
JournalCell Host and Microbe
Volume18
Issue number3
DOIs
Publication statusPublished - 9 Sept 2015

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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