Phenotypic and molecular analysis of the effect of 20-hydroxyecdysone on the human filarial parasite Brugia malayi.
Phenotypic and molecular analysis of the effect of 20-hydroxyecdysone on the human filarial parasite Brugia malayi.
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DOI：
10.1016/j.ijpara.2016.01.005
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发表时间：
2016-05
影响因子：
4
通讯作者：
Unnasch TR
中科院分区：
文献类型：
--
作者：
Mhashilkar AS;Adapa SR;Jiang RH;Williams SA;Zaky W;Slatko BE;Luck AN;Moorhead AR;Unnasch TR
蜕皮激素受体的同源物已被鉴定并显示在马来丝虫中对20-羟基蜕皮激素有反应。然而，这一昆虫发育的主要调节因子在丝虫中的作用尚未阐明。妊娠成年女性B。与对照蠕虫相比，在20-羟基蜕皮激素存在下培养的马来蠕虫产生了显著更多的微丝蚴和流产的未成熟后代，这暗示了蜕皮激素受体在胚胎发生和微丝蚴发育的调节中。转录组分析确定了30个基因的表达显着上调20-羟基蜕皮激素治疗的寄生虫与未处理的对照组相比。其中，18%被确定为调节转录。比较蛋白质组学分析显示，932蛋白质存在于更大的量在提取物中的20-羟基蜕皮激素处理的成年女性比在提取物中制备的蠕虫培养在没有激素。在20-羟基蜕皮素处理的与未处理的寄生虫提取物中表现出大于两倍差异的蛋白质中，16%参与转录调控。秀丽隐杆线虫直系同源物的RNA干扰（RNAi）表型分析显示，与胚胎发生相关的发育过程中涉及的表型显着过度表达的转录本和蛋白质，通过暴露于20-羟基蜕皮激素上调。两者合计，转录组学，蛋白质组学和表型数据表明，丝虫蜕皮激素受体可能发挥类似的作用，在昆虫中，它作为一个调节器的鸡蛋发育。
A homologue of the ecdysone receptor has been identified and shown to be responsive to 20-hydroxyecdysone in Brugia malayi. However, the role of this master regulator of insect development has not been delineated in filarial nematodes. Gravid adult female B. malayi cultured in the presence of 20-hydroxyecdysone produced significantly more microfilariae and abortive immature progeny than control worms, implicating the ecdysone receptor in regulation of embryogenesis and microfilarial development. Transcriptome analyses identified 30 genes whose expression was significantly up-regulated in 20-hydroxyecdysone-treated parasites compared with untreated controls. Of these, 18% were identified to be regulating transcription. A comparative proteomic analysis revealed 932 proteins to be present in greater amounts in extracts of 20-hydroxyecdysone-treated adult females than in extracts prepared from worms cultured in the absence of the hormone. Of the proteins exhibiting a greater than two-fold difference in the 20-hydroxyecdysone-treated versus untreated parasite extracts, 16% were involved in transcriptional regulation. RNA interference (RNAi) phenotype analysis of Caenorhabditis elegans orthologs revealed that phenotypes involved in developmental processes associated with embryogenesis were significantly over-represented in the transcripts and proteins that were up-regulated by exposure to 20-hydroxyecdysone. Taken together, the transcriptomic, proteomic and phenotypic data suggest that the filarial ecdysone receptor may play a role analogous to that in insects, where it serves as a regulator of egg development.