Cloning and characterization of an Echinococcus granulosus ecdysteroid hormone nuclear receptor HR3-like gene.

Mei Yang,Wenbao Zhang,Zhuangzhi Zhang,Xi Shou,Donald P Mcmanus,Baoping Guo,Hui Wang,Jun Wu,Fuchun Zhang,Jun Li,Chuanchuan Wu,Ning Yang

doi:10.1051/parasite/2017037

Abstract

Cystic echinococcosis is an important parasitic zoonosis caused by the dog tapeworm Echinococcus granulosus. Little is known about adult worm development at the molecular level. Transcription analysis showed that the E. granulosus hormone receptor 3-like (EgHR3) gene was expressed in protoscoleces and adult worms, indicating its role in early adult development. In this study, we cloned and characterized EgHR3 showing that its cDNA contains an open reading frame (ORF) of 1890 bp encoding a 629 amino acid protein, which has a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Immunolocalization revealed the protein was localized in the parenchyma of protoscoleces and adult worms. Real-time PCR analysis showed that EgHR3 was expressed significantly more in adults than in other stages of development (p<0.01) and that its expression was especially high in the early stage of adult worm development induced by bile acids. EgHR3 siRNA silenced 69–78% of the level of transcription in protoscoleces, which resulted in killing 43.6–60.9% of protoscoleces after 10 days of cultivation in vitro. EgHR3 may play an essential role in early adult worm development and in maintaining adult biological processes and may represent a novel drug or vaccine target against echinococcosis.

Highlights

Cystic echinococcosis (CE) is characterized by the presence of hydatid cysts in the liver, lungs or other organs in humans and herbivores
The DNA binding domain (DBD) of E. granulosus hormone receptor 3-like (EgHR3) is equipped with two zinc finger motifs and an adjacent GRIP-box [14] with a “KLGRRS” sequence at the C-terminal extension (CTE) to the DBD (Figure 1)
We identified the E. granulosus HR3like gene (EgHR3) based on its conserved structure including two zinc finger motifs containing a group of 8 cysteine residues which form the core for binding the zinc ion

Summary

Introduction

Cystic echinococcosis (CE) is characterized by the presence of hydatid cysts in the liver, lungs or other organs in humans and herbivores. CE is highly endemic in western China with prevalence ranging from 2–12% [7]. The life cycle of E. granulosus is complex, involving two mammals, including an intermediate host, usually a domestic or wild ungulate (humans are accidental hosts), and a canine definitive host (dogs, wolves). PSCs evaginate, attach to the canine intestinal mucosa, and develop into adult worms [3]. One remarkable feature of the PSC is its bidirectional development to either an adult worm (via sexual development) in the dog digestive tract, or a hydatid cyst (via asexual development) in the intermediate (or human) host. Smyth et al showed that dog bile plays a crucial role in adult worm development and sexual differentiation [8,9,10].

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Conclusion