Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum.
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.
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Sonia
S
Gulati
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Eric H
EH
Ekland
Department of Population Health, New York University School of Medicine, New York, NY 10032, USA.
Kelly V
KV
Ruggles
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Robin B
RB
Chan
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Bamini
B
Jayabalasingham
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Bowen
B
Zhou
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Pierre-Yves
PY
Mantel
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Marcus C S
MC
Lee
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Natasha
N
Spottiswoode
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Olivia
O
Coburn-Flynn
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Daisy
D
Hjelmqvist
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Tilla S
TS
Worgall
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Matthias
M
Marti
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Gilbert
G
Di Paolo
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: df2260@columbia.edu.
David A
DA
Fidock
D002853:Chromatography, Liquid; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*
D008055:Lipids