Quantitative proteomics of Trypanosoma cruzi during metacyclogenesis
Quantitative proteomics of Trypanosoma cruzi during metacyclogenesis
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DOI：
10.1002/pmic.201200078
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发表时间：
2012-08-01
期刊：
影响因子：
3.4
通讯作者：
Krieger, Marco Aurelio
中科院分区：
文献类型：
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作者：
Franco de Godoy, Lyris Martins;Marchini, Fabricio Klerynton;Krieger, Marco Aurelio
克氏锥虫是恰加斯病的病原体，据估计全世界有800多万人感染该病。克氏锥虫具有复杂的生命周期，涉及昆虫和哺乳动物宿主，并有四个不同的发育阶段：附乳突虫、亚循环乳突虫、无乳突虫和血流乳突虫。metacocygenesis是克氏T.马乳突虫向metacocyclic trypmasastigotes分化并获得传染性的过程，涉及与获得毒力相关的差异基因表达。在T. crozi中，基因表达调控主要是在转录后实现的。因此，基于蛋白质组学的方法对于在分子水平上更好地理解寄生虫阶段调节基因表达程序中发生的变化非常有用。在这里，我们对克氏T. crozi细胞元胞发生进行了深入的定量MS-based蛋白质组学研究，并量化了近3000个在分化过程中表达的蛋白质。据我们所知，这项工作是迄今为止克氏锥虫不同细胞群最全面的定量蛋白质组学研究。我们确定了参与寄生虫分化和传染性获得的相关蛋白和途径，为进一步的研究开辟了新的视角，最终可能导致确定新的化疗靶点。
Trypanosoma cruzi is the etiologic agent of Chagas disease, which is estimated to affect over eight million people around the world. Trypanosoma cruzi has a complex life cycle, involving insect and mammalian hosts and four distinct developmental stages: epimastigotes, metacyclic trypomastigotes, amastigotes, and bloodstream trypomastigotes. Metacyclogenesis is the process by which T. cruzi epimastigotes differentiate into metacyclic trypomastigotes and acquire infectivity, and involves differential gene expression associated with acquisition of virulence. In T. cruzi, gene expression regulation is achieved mainly posttranscriptionally. Therefore, proteomics-based approaches are extremely useful for gaining a better understanding of the changes that occur in the stage-regulated gene expression program of the parasite at the molecular level. Here, we performed an in-depth quantitative MS-based proteomic study of T. cruzi metacyclogenesis and quantified almost 3000 proteins expressed during the process of differentiation. To the best of our knowledge, this work is the most comprehensive quantitative proteomics study of different cell populations of T. cruzi available so far. We identified relevant proteins and pathways involved in the parasite's differentiation and infectivity acquisition, opening new perspectives for further studies that could, ultimately, lead to the identification of new targets for chemotherapy.