Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.
Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.
复制标题
DOI：
10.1371/journal.pntd.0005357
复制
发表时间：
2017-03
影响因子：
3.8
通讯作者：
Ghedin E
中科院分区：
文献类型：
--
作者：
Grote A;Voronin D;Ding T;Twaddle A;Unnasch TR;Lustigman S;Ghedin E
丝状线虫目前感染了全世界多达5400万人，还有数百万人面临感染风险，是发展中国家致残的主要原因。马来布鲁吉亚是淋巴丝虫病的病原体之一，也是唯一可以在小型实验动物体内维持的人类丝虫病寄生虫。许多丝状线虫物种，包括马来芽孢杆菌，携带专性内共生体，α -变形菌沃尔巴克氏体，可以通过抗生素治疗消除。消除内共生体会干扰蠕虫在哺乳动物宿主体内的发育、繁殖和生存，这清楚地表明沃尔巴克氏体对寄生虫的生存至关重要。人们对这种共生关系背后的机制知之甚少。为了更好地了解这两种生物之间的分子相互作用，我们通过双RNA-seq方法在寄生虫的整个生命周期中分析了马来芽胞杆菌和沃尔巴克氏体的转录组。这有助于确定线虫和细菌基因共同表达所提供的这种重要共生关系的功能途径。我们已经确定了沃尔巴克氏体在线虫发育过程中的显著阶段特异性和性别特异性差异表达。例如，在雌性蠕虫的发育过程中，我们发现沃尔巴克氏体上调了参与ATP产生和嘌呤生物合成的基因，以及参与氧化应激反应的基因。这项全球转录分析强调了沃尔巴克氏体和马来芽胞杆菌在寄生虫生命周期中同时发挥作用的特定途径，为开发新的干预策略铺平了道路。丝状线虫目前感染了全世界数百万人，是致残的主要原因。目前可用的药物不足以消除这些寄生虫。许多丝状线虫，包括马来布鲁氏线虫，都有一个致命的弱点，那就是它们与沃尔巴克氏菌的共生关系。虽然已知线虫和细菌是相互依赖的，但这种关系的分子基础仍然知之甚少。利用深度测序，我们分析了马来芽孢杆菌和沃尔巴克氏体在寄生虫整个生命周期中的转录组，以确定线虫和细菌基因共同表达所提供的寄生虫生存所必需的功能途径。确定这两种生物之间的内共生机制将允许利用这种关系来开发新的干预策略。
Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis. To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode’s development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response. This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies. Filarial nematodes currently infect millions of people worldwide and represent a leading cause of disability. Currently available medications are insufficient in reaching elimination of these parasites. Many filarial nematodes, including Brugia malayi, have an Achilles heel of sorts—that is their obligate symbiotic relationship with the bacteria Wolbachia. While it is known that the nematode and the bacteria are co-dependent, the molecular basis of this relationship remains poorly understood. Using deep sequencing, we profiled the transcriptomes of B. malayi and Wolbachia across the life cycle of the parasite to determine the functional pathways necessary for parasite survival provided by the co-expression of nematode and bacterial genes. Defining the mechanisms of endosymbiosis between these two organisms will allow for the exploitation of this relationship for the development of new intervention strategies.