Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome.
Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome.
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DOI：
10.12688/wellcomeopenres.11910.2
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发表时间：
2017
影响因子：
--
通讯作者：
Rayner J
中科院分区：
文献类型：
--
作者：
Abdi A;Yu L;Goulding D;Rono MK;Bejon P;Choudhary J;Rayner J
背景资料：许多病原体分泌效应分子以破坏宿主免疫应答、获取营养和/或为入侵准备宿主细胞。分泌效应分子的方式之一是通过细胞外囊泡（EV），如外来体。最近，疟疾寄生虫恶性疟原虫已被证明产生EV，可以介导寄生虫之间的遗传物质转移并诱导性承诺。这些囊泡的内容物的特性可能会提高我们对恶性疟原虫的发病机制和毒力的理解。 方法：以前对恶性疟原虫EV的研究仅限于长期适应的实验室分离株。在这项研究中，我们从肯尼亚恶性疟原虫临床分离株中分离出EV，该分离株已适应体外培养相对较短的时间，并通过质谱法表征其蛋白质含量（数据可通过ProteomeXchange获得，标识符为PXD 006925）。 结果如下：我们发现，恶性疟原虫细胞外囊泡（PfEVs）富含蛋白质内发现感染的红细胞，如毛雷尔裂（MC），以及分泌内膜室的裂殖子的顶端，表明PfEVs可能在寄生虫-宿主相互作用中发挥作用。将该数据集与先前发表的数据集进行比较有助于定义PfEV中存在的核心分泌组。 结论：恶性疟原虫细胞外囊泡含有毒力相关蛋白。对一系列临床分离株的PfEV含量及其功能验证的分析可能会提高我们对寄生虫毒力机制的理解，并可能确定新的干预或诊断目标。
Background: Many pathogens secrete effector molecules to subvert host immune responses, to acquire nutrients, and/or to prepare host cells for invasion. One of the ways that effector molecules are secreted is through extracellular vesicles (EVs) such as exosomes. Recently, the malaria parasite P. falciparum has been shown to produce EVs that can mediate transfer of genetic material between parasites and induce sexual commitment. Characterizing the content of these vesicles may improve our understanding of P. falciparum pathogenesis and virulence. Methods: Previous studies of P. falciparum EVs have been limited to long-term adapted laboratory isolates. In this study, we isolated EVs from a Kenyan P. falciparum clinical isolate that had been adapted to in vitro culture for a relatively shorter period, and characterized their protein content by mass spectrometry (data are available via ProteomeXchange, with identifier PXD006925). Results: We show that P. falciparum extracellular vesicles ( PfEVs) are enriched in proteins found within the exomembrane compartments of infected erythrocytes such as Maurer’s clefts (MCs), as well as the secretory endomembrane compartments in the apical end of the merozoites, suggesting that PfEVs may play a role in parasite-host interactions. Comparison of this dataset with previously published datasets helps to define a core secretome present in PfEVs. Conclusions: P. falciparum extracellular vesicles contain virulence-associated parasite proteins. Analysis of PfEVs contents from a range of clinical isolates, and their functional validation may improve our understanding of the virulence mechanisms of the parasite, and potentially identify new targets for interventions or diagnostics.