Identification of long non-coding RNAs putatively involved with Schistosoma mansoni resistance to praziquantel

• Grant number: 24/16644-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Murilo Sena Amaral
• Grantee: Pedro Jardim Poli
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes, AP.TEM

Abstract

Schistosoma mansoni is the parasite responsible for schistosomiasis in Brazil, a neglected disease that affects more than 250 million people worldwide, with the only currently recommended pharmacological treatment being the use of the drug praziquantel (PZQ). Although safe, PZQ is unable to eliminate immature worms, does not prevent reinfection, and has been used in mass administration programs, contributing to the emergence of parasite resistance. Recent studies have revealed the primary target of PZQ in S. mansoni as an ion channel from the transient receptor potential family, Sm.TRPMPZQ. The gene encoding this channel is located at QTL genomic regions in S. mansoni subpopulations with increased resistance to PZQ. However, genetic variants associated with PZQ resistance were found only in non-coding genomic regions, suggesting the contribution of other regulatory genomic elements to the PZQ resistance phenotype. In light of this, this study aims to identify long non-coding RNAs (lncRNAs) of S. mansoni potentially involved in the development of S. mansoni resistance to PZQ. LncRNAs are transcripts >200 nt with little or no protein-coding potential, involved in biological processes such as gene expression regulation, and they are linked to drug resistance development in several diseases. Specifically in S. mansoni, our group has already shown that lncRNAs are modulated under different conditions, including in vivo PZQ treatment, and that lncRNAs are crucial for the homeostasis and fertility of adult worms. From bioinformatics analyses of public data, we identified differentially expressed lncRNAs associated with the PZQ-resistant phenotype. In this project, these lncRNAs will be validated by RT-qPCR and then functionally evaluated for their involvement in the development of PZQ resistance in in vitro silencing studies. This will be the first study to identify lncRNAs potentially involved in drug resistance in a parasite and may contribute to a better understanding of PZQ resistance in S. mansoni.