Stage-specific proteomic expression patterns of the human filarial parasite Brugia malayi and its endosymbiont Wolbachia
Stage-specific proteomic expression patterns of the human filarial parasite Brugia malayi and its endosymbiont Wolbachia
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DOI：
10.1073/pnas.1011481108
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发表时间：
2011-06-07
影响因子：
11.1
通讯作者：
Nutman, Thomas B.
中科院分区：
文献类型：
--
作者：
Bennuru, Sasisekhar;Meng, Zhaojing;Nutman, Thomas B.
迄今为止，病原体的全球蛋白质组学分析仅限于单细胞生物（例如，例如，在一个实施例中，原生动物和细菌）。大多数真核生物病原体的蛋白质组学分析（e.例如，在一个实施例中，蠕虫）被限制在特定的器官、特定的阶段或分泌管中。我们在这里报告了一个大规模的蛋白质组学表征的几乎所有主要的哺乳动物阶段的马来丝虫，淋巴丝虫病的病原体，导致超过62%的产品预测从BM草案基因组的鉴定。分析还产生了沃尔巴克氏体的大部分蛋白质组，沃尔巴克氏体是Bm的专性内共生体，也以阶段特异性方式表达蛋白质。在11，610个预测的Bm基因产物中，从成年男性、成年女性、血液传播和子宫微丝蚴以及感染性L3幼虫中确定了7，103个。在从基因组推断为“假设”的4，956个基因产物（42.5%）中，本研究能够确认2，336个（47.1%）是真正的蛋白质。结合阶段特异性表达的蛋白质家族和结构域的分析突出了寄生虫在宿主中发育过程中受益的重要途径。基因集富集分析鉴定了细胞外基质蛋白和那些在微丝蚴和L3期富集的具有免疫作用的蛋白。寄生虫性别和阶段特异性蛋白表达确定了这些途径相关的寄生虫分化和展示阶段特异性表达的Bm内共生体沃尔巴克氏体以及。
Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e. g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e. g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as "hypothetical," the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex-and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont Wolbachia as well.