Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni.
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 diseas...
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ftdoajarticles:oai:doaj.org/article:9e1a5bac354f45a2b843a94e1b7f943f 2023-05-15T15:08:50+02:00 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 2021-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008770 https://doaj.org/article/9e1a5bac354f45a2b843a94e1b7f943f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008770 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008770 https://doaj.org/article/9e1a5bac354f45a2b843a94e1b7f943f PLoS Neglected Tropical Diseases, Vol 15, Iss 2, p e0008770 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008770 2022-12-31T13:53:26Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 2 e0008770 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Holly M Craven Riccardo Bonsignore Vasilis Lenis Nicolo Santi Daniel Berrar Martin Swain Helen Whiteland Angela Casini Karl F Hoffmann Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Holly M Craven Riccardo Bonsignore Vasilis Lenis Nicolo Santi Daniel Berrar Martin Swain Helen Whiteland Angela Casini Karl F Hoffmann |
author_facet |
Holly M Craven Riccardo Bonsignore Vasilis Lenis Nicolo Santi Daniel Berrar Martin Swain Helen Whiteland Angela Casini Karl F Hoffmann |
author_sort |
Holly M Craven |
title |
Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
title_short |
Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
title_full |
Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
title_fullStr |
Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
title_full_unstemmed |
Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. |
title_sort |
identifying and validating the presence of guanine-quadruplexes (g4) within the blood fluke parasite schistosoma mansoni. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0008770 https://doaj.org/article/9e1a5bac354f45a2b843a94e1b7f943f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 2, p e0008770 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008770 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008770 https://doaj.org/article/9e1a5bac354f45a2b843a94e1b7f943f |
op_doi |
https://doi.org/10.1371/journal.pntd.0008770 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
2 |
container_start_page |
e0008770 |
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1766340116969684992 |