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.
Highlights
Schistosoma mansoni, a digenean platyhelminth responsible for the neglected tropical disease (NTD) schistosomiasis, maintains its complex lifecycle through definitive human and intermediate snail (Biomphalaria sp.) hosts
Schistosoma mansoni causes schistosomiasis, a parasitic disease that affects millions of people living in resource-deprived areas of developing countries
The S. mansoni genome was searched for the presence of G4 using two different algorithms, quadparser (QP) and G4Hunter (G4h)
Summary
Schistosoma mansoni, a digenean platyhelminth responsible for the neglected tropical disease (NTD) schistosomiasis, maintains its complex lifecycle through definitive human and intermediate snail (Biomphalaria sp.) hosts. Exhibiting dioecy as adults, mature S. mansoni pairs establish infection within the human mesenteric vessels draining the intestine. While adults are largely non-immunogenic, copulation between schistosome pairs leads to the production of an estimated 300 immunogenic eggs per day. Half of these eggs migrate through the mesenteric veins and reach the intestinal lumen where they are released with faeces, a requirement for lifecycle transmission. It is estimated that some 250 million individuals worldwide suffer from schistosomiasis per annum, with the disease accounting for the loss of 2.5 million DALYs (disability adjusted life years) in 2016 [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
