Abstract
BackgroundTrichuriasis 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.MethodsThe 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.ResultsHX531 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.ConclusionsThe 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 materialThe online version of this article (doi:10.1186/1471-2334-14-520) contains supplementary material, which is available to authorized users.
Highlights
Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura
The natural ligand for retinoid X receptor (RXR) homodimers is 9-cis-retinoic acid, since RXR can heterodimerise with other nuclear hormone receptors such as the retinoic acid receptor (RAR), peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR), its ligands include all-trans-retinoic acid, fatty acids and vitamin D [7,8]
The T. muris genome contains an RXRα-like sequence Given the availability of the T. muris genome, the conserved nature of the RXR nuclear hormone receptor and the knowledge that other parasitic nematodes have retinoic acid binding capacity, the human RXRα protein sequence was queried against the T. muris gene set 2.1 (Feb 2013)
Summary
Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. The human whipworm, is an intestinal nematode affecting over 450 million people worldwide, those living in the tropics [1]. The only treatment for trichuriasis is the distribution of anthelmintics, such as mebendazole These drugs only affect the adult stage of the parasite, and resistance is becoming increasingly common; in some cases mebendazole has been reported to be as low as 45% effective [3]. The natural ligand for RXR homodimers is 9-cis-retinoic acid, since RXR can heterodimerise with other nuclear hormone receptors such as the retinoic acid receptor (RAR), peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR), its ligands include all-trans-retinoic acid, fatty acids and vitamin D [7,8]
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