Host cell phosphatidylcholine is a key mediator of malaria parasite survival during liver stage infection.
Host cell phosphatidylcholine is a key mediator of malaria parasite survival during liver stage infection.
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DOI：
10.1016/j.chom.2014.11.006
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发表时间：
2014-12-10
影响因子：
30.3
通讯作者：
Mota MM
中科院分区：
文献类型：
--
作者：
Itoe MA;Sampaio JL;Cabal GG;Real E;Zuzarte-Luis V;March S;Bhatia SN;Frischknecht F;Thiele C;Shevchenko A;Mota MM
在入侵过程中，疟疾的病原体疟原虫将自己包裹在寄生虫的空泡膜(PVM)中，该膜构成了寄生虫与其宿主细胞之间的关键界面。在肝细胞内，每个疟原虫子孢子产生数以千计的新寄生虫，产生对支持这种复制的脂类的高需求，并扩大新的PVM。在这里，对感染疟原虫的肝细胞的总脂类的全球分析显示，中性脂类和主要的膜磷脂，磷脂酰胆碱(PC)富含。虽然缺乏参与中性脂肪合成和脂肪分解的关键酶的小鼠不会受到感染的影响，但切除肝脏PC生物合成途径中的限速酶可显著减少寄生虫的数量。宿主PC由巴氏疟原虫和恶性疟原虫共同摄取，是寄生虫蛋白正确定位到PVM所必需的，PVM是寄生虫生存所必需的。因此，疟原虫依赖肝细胞内丰富的这些脂类来支持感染。伯氏疟原虫感染肝细胞的脂质组成在感染过程中发生了改变，疟原虫肝期感染不需要从头合成的中性脂类，它与PVM宿主细胞从头合成磷脂酰胆碱(PC)有关，PC的合成有助于PVM的完整性和寄生虫的生存。Itoe等人通过分析巴氏并殖吸虫感染细胞的脂质体组。揭示了磷脂酰胆碱，一种主要的膜磷脂的浓缩。靶向沉默参与新的磷脂酰胆碱合成的宿主基因表明，这些途径对疟原虫肝期感染至关重要。
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. Lipid composition of P. berghei-infected hepatocytes is altered during infection Plasmodium liver stage infection does not require de-novo-synthesized neutral lipids Plasmodium takes up host phosphatidylcholine (PC), which associates with the PVM Host cell de novo PC synthesis contributes to PVM integrity and parasite survival Plasmodium replication in hepatocytes requires abundant lipid resources. By analyzing the lipidome of P. berghei-infected cells, Itoe et al. reveal enrichment of phosphatidylcholine, a major membrane phospholipid. Targeted silencing of host genes involved in de novo phosphatidylcholine synthesis show that these pathways are critical for Plasmodium liver-stage infection.
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影响因子：
3.6
作者：
Aly, Ahmed S. I.;Mikolajczak, Sebastian A.;Rivera, Hilda Silva;Camargo, Nelly;Jacobs-Lorena, Vanessa;Labaied, Mehdi;Coppens, Isabelle;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.
DOI：
10.1074/jbc.m110.107854
发表时间：
2010-06-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chandak PG;Radovic B;Aflaki E;Kolb D;Buchebner M;Fröhlich E;Magnes C;Sinner F;Haemmerle G;Zechner R;Tabas I;Levak-Frank S;Kratky D
通讯作者：
Kratky D
影响因子：
3.6
作者：
Lindner, Scott E.;Sartain, Mark J.;Vaughan, Ashley M.
通讯作者：
Vaughan, Ashley M.
影响因子：
64.8
作者：
Mueller, AK;Labaied, M;Matuschewski, K
通讯作者：
Matuschewski, K
DOI：
10.1073/pnas.0907864106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Jao, Cindy Y.;Roth, Mary;Salic, Adrian
通讯作者：
Salic, Adrian