Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont.
Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont.
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DOI：
10.1128/mbio.02028-16
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发表时间：
2016-11-23
期刊：
影响因子：
6.4
通讯作者：
Nutman TB
中科院分区：
文献类型：
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作者：
Bennuru S;Cotton JA;Ribeiro JM;Grote A;Harsha B;Holroyd N;Mhashilkar A;Molina DM;Randall AZ;Shandling AD;Unnasch TR;Ghedin E;Berriman M;Lustigman S;Nutman TB
盘尾丝虫病（河盲症）是一种被忽视的热带疾病，美洲和非洲小部分地区的大规模药物治疗计划已成功针对该病进行治疗。然而，实现消除盘尾丝虫病的长期目标需要其他工具，包括药物、疫苗和感染生物标志物。在这里，我们描述了盘尾丝虫主要载体和人类宿主阶段（L1、L2、L3、蜕皮L3、L4、成年雄性和成年雌性）的转录组和蛋白质组谱，以及每个寄生阶段及其沃尔巴克氏体内共生体（wOv）的蛋白质组。通过这样做，我们确定了寄生虫在其早期发育过程中适应人类宿主的重要阶段特定途径。此外，我们还生成了一种蛋白质阵列，当用充分表征的人类样本进行筛选时，发现了盘旋丝虫感染的新型诊断生物标志物和新的潜在候选疫苗。这种免疫组学方法不仅展示了这种后基因组发现平台的力量，而且还为盘尾丝虫病控制计划提供了额外的工具。全球盘尾丝虫病（河盲症）消除计划必须依靠新工具（药物、疫苗、生物标志物）的开发才能在 2025 年实现其目标。作为已完成的盘尾丝虫基因组测序的辅助手段，我们使用了全面的蛋白质组和转录组分析策略来全面了解源自载体和人类宿主的寄生虫阶段。通过这样做，我们已经确定了能够进行新药物靶向研究和发现新候选疫苗以及有效感染的有用生物标志物的蛋白质和途径。
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 (wOv). 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. 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.