Wang Shuai, Wei Wei, Cai Xuepeng
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Yanchangbu, Lanzhou, 730046, Gansu, China.
Parasit Vectors. 2015 Dec 30;8:666. doi: 10.1186/s13071-015-1282-7.
The cestode Echinococcus multilocularis is the causative agent of human alveolar echinococcosis (AE). However, this life-threatening disease is still difficult to treat and control, due to the lack of efficient drugs and vaccines. Excretory/secretory (ES) proteins are crucial for parasite survival and represent potential preferred targets for novel intervention strategies. However, the ES protein features in this parasite have been poorly investigated until now. The current study was carried out to identify and characterise a repertoire of ES proteins in E. multilocularis at the genome-wide level.
Here we predicted and functionally annotated the classical and non-classical ES proteins, and comprehensively compared the features and evolution of ES and non-ES proteins in E. multilocularis genome using an integration of bioinformatics tools. The intervention target and antigen potentials as well as the transcription information were also investigated.
Computational analysis of the E. multilocularis proteins identified 673 putative ES proteins (6.4%), of which 617 (91.68%) could be supported by transcription analyses. The predicted ES proteins in E. multilocularis were mostly represented by molecular functions of protease inhibitors, proteases, glycoside hydrolases, immunoglobulin-like folds and growth factors. Analysis of the ratio between synonymous and non-synonymous substitution rates (dN/dS) revealed no significant difference of the evolution selection pressure on ES and non-ES protein coding genes. ES proteins showed higher antigenic density measured by AAR values as compared with the transmembrane proteins but had no significant difference of that feature with intracellular proteins. Additionally, 383 possible ideal drug targets were identified in ES proteins, of which four proteins have corresponding known drugs.
The present study is the first to identify a repertoire of predicted ES proteins at the genome-wide level in E. multilocularis. The comprehensive analysis provides some novel understanding of the parasite ES protein features and a valuable resource of potential targets for future experimental studies to develop new intervention tools against this parasite.
多房棘球绦虫是人类肺泡型棘球蚴病(AE)的病原体。然而,由于缺乏有效的药物和疫苗,这种危及生命的疾病仍然难以治疗和控制。排泄/分泌(ES)蛋白对寄生虫的生存至关重要,是新型干预策略潜在的首选靶点。然而,迄今为止,对该寄生虫中ES蛋白的特征研究甚少。本研究旨在在全基因组水平上鉴定和表征多房棘球绦虫的ES蛋白库。
我们预测并对经典和非经典ES蛋白进行了功能注释,并使用生物信息学工具整合,全面比较了多房棘球绦虫基因组中ES蛋白和非ES蛋白的特征及进化情况。还研究了干预靶点、抗原潜力以及转录信息。
对多房棘球绦虫蛋白的计算分析鉴定出673个推定的ES蛋白(占6.4%),其中617个(占91.68%)可得到转录分析的支持。多房棘球绦虫中预测的ES蛋白大多具有蛋白酶抑制剂、蛋白酶、糖苷水解酶、免疫球蛋白样结构域和生长因子的分子功能。同义替换率与非同义替换率之比(dN/dS)分析显示,ES蛋白和非ES蛋白编码基因的进化选择压力无显著差异。与跨膜蛋白相比,通过AAR值测量,ES蛋白显示出更高的抗原密度,但与细胞内蛋白在该特征上无显著差异。此外,在ES蛋白中鉴定出383个可能的理想药物靶点,其中4种蛋白有相应的已知药物。
本研究首次在全基因组水平上鉴定了多房棘球绦虫预测的ES蛋白库。综合分析为寄生虫ES蛋白特征提供了一些新的认识,并为未来开发针对该寄生虫的新干预工具的实验研究提供了潜在靶点的宝贵资源。