Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni

Holly M Craven, Riccardo Bonsignore, Vasilis Lenis, Nicolo Santi, Daniel Berrar, Martin Swain, Helen Whiteland, Angela Casini, Karl F Hoffmann

Research output: Contribution to journalArticlepeer-review

Abstract

Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regions of the seven autosomes as well as the sex-defining allosome pair. Amongst intragenic regions, G4 are particularly enriched in 3´ UTR regions. Gene Ontology (GO) term analysis evidenced significant G4 enrichment in the wnt signalling pathway (p<0.05) and PQS oligonucleotides synthetically derived from wnt-related genes resolve into parallel and anti-parallel G4 motifs as elucidated by circular dichroism (CD) spectroscopy. Finally, utilising a single chain anti-G4 antibody called BG4, we confirm the in situ presence of G4 within both adult female and male worm nuclei. These results collectively suggest that G4-targeted compounds could be tested as novel anthelmintic agents and highlights the possibility that G4-stabilizing molecules could be progressed as candidates for the treatment of schistosomiasis.

Original languageEnglish
Article numbere0008770
Pages (from-to)1-24
Number of pages24
JournalPLoS Neglected Tropical Diseases
Volume15
Issue number2
DOIs
Publication statusPublished - 18 Feb 2021
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded in whole, or in part, by the Wellcome Trust [Grant number 107475/Z/15/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The work was additionally funded by Aberystwyth University (https://www.aber.ac.uk/en/) and the Joy Welch Educational Charitable Trust.

Publisher Copyright:
© 2021 Craven et al.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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