A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing

Publication date: Available online 5 April 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): George Cherian Pandarakalam, Michael Speake, Stuart McElroy, Ammar Alturkistani, Lucas Phillipe, Jonathan Pettitt, Berndt Müller, Bernadette ConnollyAbstractInfections with parasitic nematodes are among the most significant of the neglected tropical diseases affecting about a billion people living mainly in tropical regions with low economic activity.The most effective current strategy to control nematode infections involves large scale treatment programs with anthelmintic drugs. This strategy is at risk from the emergence of drug resistant parasites. Parasitic nematodes also affect livestock, which are treated with the same limited group of anthelmintic drugs. Livestock parasites resistant to single drugs, and even multi-drug resistant parasites, are appearing in many areas. There is therefore a pressing need for new anthelmintic drugs.Here we use the nematode Caenorhabditis elegans as a model for parasitic nematodes and demonstrate that sinefungin, a competitive inhibitor of methyltransferases, causes a delay in development and reduced fertility, and inhibits spliced leader trans-splicing. Spliced leader trans-splicing is an essential step in gene expression that does not occur in the hosts of parasitic nematodes, and is therefore a potential target for new anthelmintic drugs.We have exploited the ability of sinefungin to inhibit spliced leader...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research