Genome-wide analysis of excretory/secretory proteins in Echinococcus multilocularis: insights into functional characteristics of the tapeworm secretome

Shuai Wang, Wei, Xuepeng Cai

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.