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Host Cell Phosphatidylcholine Is a Key Mediator of Malaria Parasite Survival during Liver Stage Infection
被引:86
作者:

Itoe, Maurice A.
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Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Sampaio, Julio L.
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Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Cabal, Ghislain G.
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Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Real, Eliana
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Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Zuzarte-Luis, Vanessa
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Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

March, Sandra
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机构:
MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
MIT, Koch Inst, Cambridge, MA 02139 USA Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Bhatia, Sangeeta N.
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机构:
MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
MIT, Koch Inst, Cambridge, MA 02139 USA Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

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Thiele, Christoph
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机构:
Univ Bonn, Lab Biochem & Cell Biol Lipids, Life & Med Sci Inst, D-53115 Bonn, Germany Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

Shevchenko, Andrej
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Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

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机构:
[1] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal
[2] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
[3] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
[4] MIT, Koch Inst, Cambridge, MA 02139 USA
[5] Heidelberg Univ, Sch Med, Dept Infect Dis, D-69120 Heidelberg, Germany
[6] Univ Bonn, Lab Biochem & Cell Biol Lipids, Life & Med Sci Inst, D-53115 Bonn, Germany
基金:
欧洲研究理事会;
关键词:
ADIPOSE TRIGLYCERIDE LIPASE;
PLASMODIUM-FALCIPARUM;
PARASITOPHOROUS VACUOLE;
TARGETED DELETION;
MEMBRANE-LIPIDS;
SPOROZOITES;
STEATOHEPATITIS;
PHOSPHOLIPIDS;
PHAGOCYTOSIS;
METABOLISM;
D O I:
10.1016/j.chom.2014.11.006
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
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.
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页码:778 / 786
页数:9
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