Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production.
Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual mat...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0005994 https://doaj.org/article/bacaa2ac7d364a01a33cfbf94adc8cb1 |
id |
ftdoajarticles:oai:doaj.org/article:bacaa2ac7d364a01a33cfbf94adc8cb1 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:bacaa2ac7d364a01a33cfbf94adc8cb1 2023-05-15T15:12:57+02:00 Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. Alessandra Guidi Cristiana Lalli Roberto Gimmelli Emanuela Nizi Matteo Andreini Nadia Gennari Fulvio Saccoccia Steven Harper Alberto Bresciani Giovina Ruberti 2017-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005994 https://doaj.org/article/bacaa2ac7d364a01a33cfbf94adc8cb1 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5646872?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005994 https://doaj.org/article/bacaa2ac7d364a01a33cfbf94adc8cb1 PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0005994 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005994 2022-12-31T07:08:20Z Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual maturation of the female. Pairing is required for the full development of the two major female organs, ovary and vitellarium that are involved in the production of different cell types such as oocytes and vitellocytes, which represent the core elements of the whole egg machinery. Sexually mature females can produce a large number of eggs each day. Due to the importance of egg production for both life cycle and pathogenesis, there is significant interest in the search for new strategies and compounds not only affecting parasite viability but also egg production. Here we use a recently developed high-throughput organism-based approach, based on ATP quantitation in the schistosomula larval stage of Schistosoma mansoni for the screening of a large compound library, and describe a pharmacophore-based drug selection approach and phenotypic analyses to identify novel multi-stage schistosomicidal compounds. Interestingly, worm pairs treated with seven of the eight compounds identified show a phenotype characterized by defects in eggshell assemblage within the ootype and egg formation with degenerated oocytes and vitelline cells engulfment in the uterus and/or oviduct. We describe promising new molecules that not only impair the schistosomula larval stage but also impact juvenile and adult worm viability and egg formation and production in vitro. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 10 e0005994 |
institution |
Open Polar |
collection |
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 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Alessandra Guidi Cristiana Lalli Roberto Gimmelli Emanuela Nizi Matteo Andreini Nadia Gennari Fulvio Saccoccia Steven Harper Alberto Bresciani Giovina Ruberti Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual maturation of the female. Pairing is required for the full development of the two major female organs, ovary and vitellarium that are involved in the production of different cell types such as oocytes and vitellocytes, which represent the core elements of the whole egg machinery. Sexually mature females can produce a large number of eggs each day. Due to the importance of egg production for both life cycle and pathogenesis, there is significant interest in the search for new strategies and compounds not only affecting parasite viability but also egg production. Here we use a recently developed high-throughput organism-based approach, based on ATP quantitation in the schistosomula larval stage of Schistosoma mansoni for the screening of a large compound library, and describe a pharmacophore-based drug selection approach and phenotypic analyses to identify novel multi-stage schistosomicidal compounds. Interestingly, worm pairs treated with seven of the eight compounds identified show a phenotype characterized by defects in eggshell assemblage within the ootype and egg formation with degenerated oocytes and vitelline cells engulfment in the uterus and/or oviduct. We describe promising new molecules that not only impair the schistosomula larval stage but also impact juvenile and adult worm viability and egg formation and production in vitro. |
format |
Article in Journal/Newspaper |
author |
Alessandra Guidi Cristiana Lalli Roberto Gimmelli Emanuela Nizi Matteo Andreini Nadia Gennari Fulvio Saccoccia Steven Harper Alberto Bresciani Giovina Ruberti |
author_facet |
Alessandra Guidi Cristiana Lalli Roberto Gimmelli Emanuela Nizi Matteo Andreini Nadia Gennari Fulvio Saccoccia Steven Harper Alberto Bresciani Giovina Ruberti |
author_sort |
Alessandra Guidi |
title |
Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
title_short |
Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
title_full |
Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
title_fullStr |
Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
title_full_unstemmed |
Discovery by organism based high-throughput screening of new multi-stage compounds affecting Schistosoma mansoni viability, egg formation and production. |
title_sort |
discovery by organism based high-throughput screening of new multi-stage compounds affecting schistosoma mansoni viability, egg formation and production. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005994 https://doaj.org/article/bacaa2ac7d364a01a33cfbf94adc8cb1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 10, p e0005994 (2017) |
op_relation |
http://europepmc.org/articles/PMC5646872?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005994 https://doaj.org/article/bacaa2ac7d364a01a33cfbf94adc8cb1 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005994 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
10 |
container_start_page |
e0005994 |
_version_ |
1766343559998341120 |