Host-parasite interactions revealed by Plasmodium falciparum metabolomics.
Host-parasite interactions revealed by Plasmodium falciparum metabolomics.
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DOI：
10.1016/j.chom.2009.01.004
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发表时间：
2009-02-19
影响因子：
30.3
通讯作者：
Llinás M
中科院分区：
文献类型：
--
作者：
Olszewski KL;Morrisey JM;Wilinski D;Burns JM;Vaidya AB;Rabinowitz JD;Llinás M
细胞内病原体已经设计出利用宿主细胞的机制，以确保它们的生存和复制。恶性疟原虫依靠与宿主交换代谢物来增殖。我们描述了寄生虫在其48小时红细胞内发育周期的第一个基于质谱的代谢组学分析。我们的研究结果揭示了寄生虫对代谢物水平的一般调节，许多代谢物随发育周期而变化。其他细胞与未感染的细胞不同，与发育阶段无关。其中包括细胞外精氨酸，它被寄生虫特异性地转化为鸟氨酸。为了确定这种作用的生化基础，我们破坏了啮齿动物疟疾模型伯氏疟原虫精氨酸酶基因。这些寄生虫是有活力的，但不能将精氨酸转化为鸟氨酸。我们的研究结果表明，寄生虫的系统性精氨酸消耗可能是与脑型疟疾发病机制相关的人疟疾低精氨酸血症的一个因素。
Intracellular pathogens have devised mechanisms to exploit their host cells to ensure their survival and replication. The malaria parasite Plasmodium falciparum relies on an exchange of metabolites with the host for proliferation. We describe the first mass spectrometry-based metabolomic analysis of the parasite throughout its 48-hour intraerythrocytic developmental cycle. Our results reveal a general modulation of metabolite levels by the parasite, with numerous metabolites varying in phase with the developmental cycle. Others differed from uninfected cells irrespective of the developmental stage. Among these was extracellular arginine, which was specifically converted to ornithine by the parasite. To identify the biochemical basis for this effect, we disrupted the plasmodium arginase gene in the rodent malaria model P. berghei. These parasites were viable but did not convert arginine to ornithine. Our results suggest that systemic arginine depletion by the parasite may be a factor in human malarial hypoargininemia associated with cerebral malaria pathogenesis.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
82.9
作者：
Gramaglia, Irene;Sobolewski, Peter;van der Heyde, Henri C.
通讯作者：
van der Heyde, Henri C.
影响因子：
3.6
作者：
Foth, BJ;Stimmler, LM;McFadden, GI
通讯作者：
McFadden, GI
影响因子：
20.3
作者：
Kleinbongard, P;Schulz, R;Kelm, M
通讯作者：
Kelm, M
影响因子：
168.9
作者：
Lopansri, BK;Anstey, NM;Granger, DL
通讯作者：
Granger, DL