Journal
ACTA TROPICA
Volume 221, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.actatropica.2021.105991
Keywords
Echinococcus granulosus s; l; Glutathione transferases; Immunolocalization; Gene expression; Experimental infection
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Funding
- Universidad de la Republica (CSIC, Uruguay)
- ANII (Uruguay)
- PEDECIBA (Uruguay)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
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The study revealed the important roles of GSTs in E. granulosus s.l. biology, particularly in parasite establishment and detoxification processes. EgGST1 was found to be associated with detoxification, with increased expression in the parenchyma of pre-adult protoscoleces (PSCs); EgGST2, located on the tegument of PSCs, showed increased expression post-anthelmintic treatment, potentially related to immunoregulation and chemotherapy resistance; EgGST3, related to the Omega class, exhibited distribution throughout the PSC body and increased expression in response to oxidative stress.
Glutathione transferases (GSTs) belong to a diverse superfamily of multifunctional proteins involved in metabolic detoxification. In helminth parasite, GSTs are particularly relevant since they are also involved in host immunomodulation. Echinococcus granulosus sensu lato (s.l.) is a cestode parasite known to express at least three phylogenetically distant cytosolic GSTs: EgGST1 and EgGST2 previously grouped within Mu and Sigma classes, respectively; and EgGST3 related to both Omega and Sigma classes. To better characterize E. granulosus s.l. GSTs, herein their expression and distribution were assessed in the pre-adult protoscolex (PSC) parasite stage. Potential transcriptional regulatory mechanisms of the corresponding EgGST genes were also explored. Firstly, the transcription of the three EgGSTs was significantly induced during the early stages of the murine model of infection, suggesting a potential role during parasite establishment. EgGST1 was detected in the parenchyma of PSCs and its expression increased after H2O2 exposure, supporting its role in detoxification. EgGST2 was mainly detected on the PSCs tegument, strategically localized for potential immunoregulation functions due to its Sigma-class characteristics. In addition, its expression increased after anthelmintic treatment, suggesting a role in chemotherapy resistance. Finally, the Omega-related EgGST3 was localized throughout the entire PSC body, including suckers and tegument, and since its expression also increased after H2O2 treatment, a potential role in oxidative stress response could also be ascribed. On the other hand, known cis-acting regulatory motifs were detected in EgGST genes, suggesting similar transcription processes to other eukaryotes. The results herein reported provide additional data regarding the roles of EgGSTs in E. granulosus s.l. biology, contributing to a better understanding of its host-parasite interaction.
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