title: Host cell phosphatidylcholine is a key mediator of malaria parasite survival during liver stage infection.
abstract: During invasion, Plasmodium, the causative agent of malaria, wraps itself in a parasitophorous vacuole membrane (PVM), which constitutes a critical interface between the parasite and its host cell. Within hepatocytes, each Plasmodium sporozoite generates thousands of new parasites, creating high demand for lipids to support this replication and enlarge the PVM. Here, a global analysis of the total lipid repertoire of Plasmodium-infected hepatocytes reveals an enrichment of neutral lipids and the major membrane phospholipid, phosphatidylcholine (PC). While infection is unaffected in mice deficient in key enzymes involved in neutral lipid synthesis and lipolysis, ablation of rate-limiting enzymes in hepatic PC biosynthetic pathways significantly decreases parasite numbers. Host PC is taken up by both P. berghei and P. falciparum and is necessary for correct localization of parasite proteins to the PVM, which is essential for parasite survival. Thus, Plasmodium relies on the abundance of these lipids within hepatocytes to support infection.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Itoe
authors.affiliation: Max Planck Institute of Molecular cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Júlio L
authors.initials: JL
authors.lastname: Sampaio
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Ghislain G
authors.initials: GG
authors.lastname: Cabal
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Eliana
authors.initials: E
authors.lastname: Real
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zuzarte-Luis
authors.affiliation: Institute for Medical Engineering and Science/Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: March
authors.affiliation: Institute for Medical Engineering and Science/Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
authors.affiliation: Department of Infectious Diseases, University of Heidelberg Medical School, 69120 Heidelberg, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Frischknecht
authors.affiliation: Laboratory of Biochemistry and Cell Biology of Lipids, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiele
authors.affiliation: Max Planck Institute of Molecular cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. Electronic address: mmota@medicina.ulisboa.pt.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000469:parasitology*; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010962:Plasmodium berghei / Q000254:growth & development / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D034101:Sporozoites / Q000254:growth & development / Q000378:metabolism
chemical_list: D010713:Phosphatidylcholines