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Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

机译:丝状寄生虫肠球菌及其 Wolbachia 内共生体的特定阶段转录组和蛋白质组分析

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ABSTRACT Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont ( w Ov). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O.?volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. IMPORTANCE The global onchocerciasis (river blindness) elimination program will have to rely on the development of new tools (drugs, vaccines, biomarkers) to achieve its goals by 2025. As an adjunct to the completed genomic sequencing of O.?volvulus , we used a comprehensive proteomic and transcriptomic profiling strategy to gain a comprehensive understanding of both the vector-derived and human host-derived parasite stages. In so doing, we have identified proteins and pathways that enable novel drug targeting studies and the discovery of novel vaccine candidates, as well as useful biomarkers of active infection.
机译:摘要盘尾丝虫病(河盲症)是一种被忽视的热带病,已在美洲和非洲一小部分地区通过大规模药物治疗计划成功靶向。但是,要实现消除盘尾丝虫病的长期目标,还需要其他工具,包括药物,疫苗和感染的生物标志物。在这里,我们描述了Onchocerca volvulus主要载体和人类宿主阶段(L1,L2,L3,蜕皮的L3,L4,成年雄性和成年雌性)的转录组和蛋白质组谱,以及每个寄生虫阶段和其Wolbachia内共生体(w Ov)。通过这样做,我们已经确定了特定阶段的途径,这对于寄生虫在其早期发育过程中适应其宿主具有重要意义。此外,我们生成了一种蛋白质阵列,当用特征明确的人类样品进行筛选时,可以鉴定出食虫链球菌感染的新型诊断生物标志物和新的潜在疫苗候选物。这种免疫学方法不仅证明了该基因组后发现平台的功能,而且还为盘尾丝虫病控制程序提供了其他工具。重要事项全球消除盘尾丝虫病(河盲)计划将不得不依靠新工具(药物,疫苗,生物标记物)的开发来实现其到2025年的目标。作为完成volv线虫基因组测序的辅助手段,我们使用了全面的蛋白质组学和转录组学分析策略,以全面了解载体来源和人类宿主来源的寄生虫阶段。通过这样做,我们确定了能够进行新型药物靶向研究和发现新型疫苗候选物的蛋白质和途径,以及有效的主动感染生物标记。

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