Brinkman Diane L, Jia Xinying, Potriquet Jeremy, Kumar Dhirendra, Dash Debasis, Kvaskoff David, Mulvenna Jason
Australian Institute of Marine Science, Townsville, QLD, Australia.
Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
BMC Genomics. 2015 May 27;16(1):407. doi: 10.1186/s12864-015-1568-3.
The box jellyfish, Chironex fleckeri, is the largest and most dangerous cubozoan jellyfish to humans. It produces potent and rapid-acting venom and its sting causes severe localized and systemic effects that are potentially life-threatening. In this study, a combined transcriptomic and proteomic approach was used to identify C. fleckeri proteins that elicit toxic effects in envenoming.
More than 40,000,000 Illumina reads were used to de novo assemble ∼ 34,000 contiguous cDNA sequences and ∼ 20,000 proteins were predicted based on homology searches, protein motifs, gene ontology and biological pathway mapping. More than 170 potential toxin proteins were identified from the transcriptome on the basis of homology to known toxins in publicly available sequence databases. MS/MS analysis of C. fleckeri venom identified over 250 proteins, including a subset of the toxins predicted from analysis of the transcriptome. Potential toxins identified using MS/MS included metalloproteinases, an alpha-macroglobulin domain containing protein, two CRISP proteins and a turripeptide-like protease inhibitor. Nine novel examples of a taxonomically restricted family of potent cnidarian pore-forming toxins were also identified. Members of this toxin family are potently haemolytic and cause pain, inflammation, dermonecrosis, cardiovascular collapse and death in experimental animals, suggesting that these toxins are responsible for many of the symptoms of C. fleckeri envenomation.
This study provides the first overview of a box jellyfish transcriptome which, coupled with venom proteomics data, enhances our current understanding of box jellyfish venom composition and the molecular structure and function of cnidarian toxins. The generated data represent a useful resource to guide future comparative studies, novel protein/peptide discovery and the development of more effective treatments for jellyfish stings in humans. (Length: 300).
箱形水母,即澳大利亚箱形水母(Chironex fleckeri),是对人类来说体型最大且最危险的立方水母。它能产生强效且作用迅速的毒液,其蜇刺会引发严重的局部和全身效应,有潜在的生命危险。在本研究中,采用了转录组学和蛋白质组学相结合的方法来鉴定在蜇伤中毒时引发毒性效应的澳大利亚箱形水母蛋白质。
超过4000万条Illumina测序读数用于从头组装约34000个连续的cDNA序列,并基于同源性搜索、蛋白质基序、基因本体和生物途径映射预测了约20000种蛋白质。基于与公开可用序列数据库中已知毒素的同源性,从转录组中鉴定出170多种潜在毒素蛋白。对澳大利亚箱形水母毒液的串联质谱分析鉴定出250多种蛋白质,包括从转录组分析预测出的一部分毒素。通过串联质谱鉴定出的潜在毒素包括金属蛋白酶、一种含有α-巨球蛋白结构域的蛋白质、两种富含半胱氨酸的分泌性蛋白质(CRISP)和一种类turripeptide蛋白酶抑制剂。还鉴定出了一个分类学上受限的强效刺胞动物成孔毒素家族的九个新成员。该毒素家族的成员具有很强的溶血作用,并在实验动物中引起疼痛、炎症、皮肤坏死、心血管衰竭和死亡,这表明这些毒素是导致澳大利亚箱形水母蜇伤许多症状的原因。
本研究首次概述了箱形水母的转录组,结合毒液蛋白质组学数据,增强了我们目前对箱形水母毒液组成以及刺胞动物毒素的分子结构和功能的理解。所生成的数据是指导未来比较研究、发现新型蛋白质/肽以及开发更有效治疗人类水母蜇伤方法的有用资源。(长度:300)