BackgroundThe lack of new anthelmintic agents is of growing concern because it affects human health and our food supply, as both livestock and plants are affected. Two principal factors contribute to this problem. First, nematode resistance to anthelmintic drugs is increasing worldwide and second, many effective nematicides pose environmental hazards. In this paper we address this problem by deploying a high throughput screening platform for anthelmintic drug discovery using the nematode Caenorhabditis elegans as a surrogate for infectious nematodes. This method offers the possibility of identifying new anthelmintics in a cost-effective and timely manner.Methods/Principal findingsUsing our high throughput screening platform we have identified 14 new potential anthelmintics by screening more than 26,000 compounds from the Chembridge and Maybridge chemical libraries. Using phylogenetic profiling we identified a subset of the 14 compounds as potential anthelmintics based on the relative sensitivity of C. elegans when compared to yeast and mammalian cells in culture. We showed that a subset of these compounds might employ mechanisms distinct from currently used anthelmintics by testing diverse drug resistant strains of C. elegans. One of these newly identified compounds targets mitochondrial complex II, and we used structural analysis of the target to suggest how differential binding of this compound may account for its different effects in nematodes versus mammalian cells.Conclusions/SignificanceThe challenge of anthelmintic drug discovery is exacerbated by several factors; including, 1) the biochemical similarity between host and parasite genomes, 2) the geographic location of parasitic nematodes and 3) the rapid development of resistance. Accordingly, an approach that can screen large compound collections rapidly is required. C. elegans as a surrogate parasite offers the ability to screen compounds rapidly and, equally importantly, with specificity, thus reducing the potential toxicity of these compounds to the host and the environment. We believe this approach will help to replenish the pipeline of potential nematicides.
Long before the exacerbating effects of COVID-19, household food insecurity (HFI) has been a persistent yet hidden problem in wealthy nations such as Canada, where it has been perpetuated in part through dominant discourses and practices. In this critique of HFI-related frameworks, we suggest that discourses organized around the production and (re)distribution of food, rather than income inequality, have misdirected household food insecurity reduction activities away from the central issue of poverty, even inadvertently enabling the ongoing neoliberal “rollback” of safety net functions. Unlike most scholarship that focuses on the politics of food systems, or health research that insufficiently politicizes poverty, this analysis emphasizes the role of politics in income discourses. In spite of their contradictions, food-provisioning- and income-based discourses are potentially complementary in their shared recognition of the right to food. Operating from the perspective of political economic theory, we conceive of the right to food as a claim not only to a resource but also to membership within political communities that envision alternatives to neoliberalism as manifested in our labour, welfare, and food systems. In this sense, the right to food offers a unifying framework that links civil society with senior governments, collective action with legal instruments, and food and income concerns. HFI reduction activities organized around the right to food may thus aim to rectify cross-cutting imbalances in political and economic power.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.