TY - JOUR
T1 - Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum
AU - Gulati, Sonia
AU - Ekland, Eric H.
AU - Ruggles, Kelly V.
AU - Chan, Robin B.
AU - Jayabalasingham, Bamini
AU - Zhou, Bowen
AU - Mantel, Pierre Yves
AU - Lee, Marcus C.S.
AU - Spottiswoode, Natasha
AU - Coburn-Flynn, Olivia
AU - Hjelmqvist, Daisy
AU - Worgall, Tilla S.
AU - Marti, Matthias
AU - Di Paolo, Gilbert
AU - Fidock, David A.
N1 - Funding Information:
Funding for this work was provided by the NIH (R01 AI085584 and R01 AI103058 to D.A.F), a postdoctoral award from Novartis for P.-Y.M., and a Burroughs Wellcome carrier development award for M.M.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/9/9
Y1 - 2015/9/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84941280668&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.08.003
DO - 10.1016/j.chom.2015.08.003
M3 - Article
C2 - 26355219
AN - SCOPUS:84941280668
SN - 1931-3128
VL - 18
SP - 371
EP - 381
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -