AUTHOR=Batista Izabella Cristina Andrade , Gava Sandra Grossi , Tavares Naiara Clemente , Calzavara-Silva Carlos Eduardo , Mourão Marina Moraes 

TITLE=Hypoxanthine guanine phosphoribosyl transferases SmHGPRTases functional roles in Schistosoma mansoni

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1064218

DOI=10.3389/fmicb.2022.1064218

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Extracellular/environmental stimuli trigger cellular responses to allow <italic>Schistosoma</italic> 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 <italic>Schistosoma mansoni</italic> 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 (<italic>SmHGPRTase</italic> 1, Smp_103560), a key enzyme in the purine salvage pathway that is part of a family comprising five different proteins.</p></sec><sec><title>Methods</title><p>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 <italic>HGPRTases</italic> (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.</p></sec><sec><title>Results</title><p>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 <italic>in vitro</italic> knockdown. Also, the knockdown of <italic>SmHGPRTases</italic> 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 <italic>in vitro</italic>. Most of these results were shown when all gene family members were knocked-down simultaneously, suggesting a redundant function among them.</p></sec><sec><title>Discussion</title><p>Thus, this study helps to elucidate the functional roles of the <italic>SmHGPRTase</italic> gene family in the <italic>S. mansoni</italic> life cycle and provides knowledge for future studies required for schistosomiasis treatment and control.</p></sec>