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An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro

BACKGROUND: Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment...

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Autores principales: Hurst, Rebecca JM, Hopwood, Thomas, Gallagher, Amanda L, Partridge, Frederick A, Burgis, Timothy, Sattelle, David B, Else, Kathryn J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261559/
https://www.ncbi.nlm.nih.gov/pubmed/25261877
http://dx.doi.org/10.1186/1471-2334-14-520
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author Hurst, Rebecca JM
Hopwood, Thomas
Gallagher, Amanda L
Partridge, Frederick A
Burgis, Timothy
Sattelle, David B
Else, Kathryn J
author_facet Hurst, Rebecca JM
Hopwood, Thomas
Gallagher, Amanda L
Partridge, Frederick A
Burgis, Timothy
Sattelle, David B
Else, Kathryn J
author_sort Hurst, Rebecca JM
collection PubMed
description BACKGROUND: Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment relies mainly on general anthelmintics such as mebendazole but resistance to these drugs is increasingly problematic. Therefore, new treatments are urgently required. METHODS: The prospect of using the retinoid X receptor (RXR) antagonist HX531 as a novel anthelmintic was investigated by carrying out multiple viability assays with the mouse whipworm Trichuris muris. RESULTS: HX531 reduced both the motility and viability of T. muris at its L3, L4 and adult stages. Further, bioinformatic analyses show that the T. muris genome possesses an RXR-like receptor, a possible target for HX531. CONCLUSIONS: The study suggested that Trichuris-specific RXR antagonists may be a source of much-needed novel anthelmintic candidates for the treatment of trichuriasis. The identification of an RXR-like sequence in the T. muris genome also paves the way for further research based on this new anthelmintic lead compound. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-520) contains supplementary material, which is available to authorized users.
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spelling pubmed-42615592014-12-10 An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro Hurst, Rebecca JM Hopwood, Thomas Gallagher, Amanda L Partridge, Frederick A Burgis, Timothy Sattelle, David B Else, Kathryn J BMC Infect Dis Research Article BACKGROUND: Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment relies mainly on general anthelmintics such as mebendazole but resistance to these drugs is increasingly problematic. Therefore, new treatments are urgently required. METHODS: The prospect of using the retinoid X receptor (RXR) antagonist HX531 as a novel anthelmintic was investigated by carrying out multiple viability assays with the mouse whipworm Trichuris muris. RESULTS: HX531 reduced both the motility and viability of T. muris at its L3, L4 and adult stages. Further, bioinformatic analyses show that the T. muris genome possesses an RXR-like receptor, a possible target for HX531. CONCLUSIONS: The study suggested that Trichuris-specific RXR antagonists may be a source of much-needed novel anthelmintic candidates for the treatment of trichuriasis. The identification of an RXR-like sequence in the T. muris genome also paves the way for further research based on this new anthelmintic lead compound. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-520) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-27 /pmc/articles/PMC4261559/ /pubmed/25261877 http://dx.doi.org/10.1186/1471-2334-14-520 Text en © Hurst et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hurst, Rebecca JM
Hopwood, Thomas
Gallagher, Amanda L
Partridge, Frederick A
Burgis, Timothy
Sattelle, David B
Else, Kathryn J
An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title_full An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title_fullStr An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title_full_unstemmed An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title_short An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro
title_sort antagonist of the retinoid x receptor reduces the viability of trichuris muris in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261559/
https://www.ncbi.nlm.nih.gov/pubmed/25261877
http://dx.doi.org/10.1186/1471-2334-14-520
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