Dataset Information

Hypoxanthine guanine phosphoribosyl transferases SmHGPRTases functional roles in Schistosoma mansoni.

ABSTRACT:

Introduction

Extracellular/environmental stimuli trigger cellular responses to allow Schistosoma sp. parasites adaptation and decide development and survival fate. In this context, signal transduction involving eukaryotic protein kinases (ePKs) has an essential role in regulatory mechanisms. Functional studies had shown the importance of MAPK pathway for Schistosoma mansoni development. In addition, early studies demonstrated that Smp38 MAPK regulates the expression of a large set of genes, among them the hypoxanthine-guanine phosphoribosyl transferase 1 (SmHGPRTase 1, Smp_103560), a key enzyme in the purine salvage pathway that is part of a family comprising five different proteins.

Methods

First, the regulation of this gene family by the MAPKs pathways was experimentally verified using Smp38-predicted specific inhibitors. In silico analysis showed significant differences in the predicted structure and the domain sequence among the schistosomal HGPRTase family and their orthologs in humans. In order to interrogate the HGPRTases (Smp_103560, Smp_148820, Smp_168500, Smp_312580 and Smp_332640, henceforth SmHGPRTase -1, -2, -3, -4, -5) functional roles, schistosomula, sporocysts, and adult worms were knocked-down using specific dsRNAs.

Results

Our results suggest that SmHGPRTases activity has an essential role in sporocysts and schistosomula development since significant differences in viability, size, and/ or shape were observed after the in vitro knockdown. Also, the knockdown of SmHGPRTases in schistosomula influenced the ovary development and egg maturation in female adult worms during mammalian infection. We also observed alterations in the movement of female adult worms knocked-down in vitro. Most of these results were shown when all gene family members were knocked-down simultaneously, suggesting a redundant function among them.

Discussion

Thus, this study helps to elucidate the functional roles of the SmHGPRTase gene family in the S. mansoni life cycle and provides knowledge for future studies required for schistosomiasis treatment and control.

SUBMITTER: Batista ICA

PROVIDER: S-EPMC9791060 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Hypoxanthine guanine phosphoribosyl transferases SmHGPRTases functional roles in <i>Schistosoma mansoni</i>.

Batista Izabella Cristina Andrade ICA Gava Sandra Grossi SG Tavares Naiara Clemente NC Calzavara-Silva Carlos Eduardo CE Mourão Marina Moraes MM

Frontiers in microbiology 20221212

<h4>Introduction</h4>Extracellular/environmental stimuli trigger cellular responses to allow <i>Schistosoma</i> sp. parasites adaptation and decide development and survival fate. In this context, signal transduction involving eukaryotic protein kinases (ePKs) has an essential role in regulatory mechanisms. Functional studies had shown the importance of MAPK pathway for <i>Schistosoma mansoni</i> development. In addition, early studies demonstrated that Smp38 MAPK regulates the expression of a la ...[more]

PMID: 36578572

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