Biology subjects

Redman, E. M.

Publications and source records attributed to Redman, E. M..

4 recordsLinked to original sources

bioRxiv2022

Selective Control of Parasitic Nematodes Using Bioactivated Nematicides

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amidst limited arable land. Most traditional nematicides have been banned due to poor nematode-selectivity, leaving farmers with inadequate controls. Here, we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome p450-dependent bioactivation exclusively in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita - the worlds most destructive plant-parasitic nematode. Tests against a wide range of phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than nearly all marketed nematicides. Thus, selectivins are first-in-class bioactivated nematode controls that provide efficacy as well as much-needed nematode selectivity.

pharmacology and toxicology↗

bioRxiv2022

A Nematode-Selective Potentiator of Organophosphate and Carbamate Agrochemicals

Nematode parasites of humans, livestock and crops pose a significant burden on human health and welfare. Alarmingly, parasitic nematodes of animals have rapidly evolved resistance to anthelmintic drugs, and traditional nematicides that protect crops are facing increasing restrictions because of poor phylogenetic selectivity. Here, we present a pipeline that exploits multiple motor outputs of the model nematode C. elegans for nematicide discovery. This pipeline yielded multiple compounds that selectively kill and/or immobilize diverse nematode parasites. We focus on one compound that induces violent convulsions and paralysis that we call Nementin. We find that Nementin agonizes neuronal dense core vesicle release, which in turn agonizes cholinergic signaling. Consequently, Nementin synergistically enhances the potency of widely-used non-selective acetylcholinesterase inhibitors (AChEIs), but in a nematode-selective manner. Nementin therefore has the potential to reduce the environmental impact of toxic AChEI pesticides used to control nematode infections and infestations. Significance StatementParasitic nematodes pose a considerable burden to human health and food security. Small molecules that have traditionally been used to control these parasites have either been banned because of toxicity concerns or are being rendered ineffective because of the evolution of resistance. Significant gaps in our nematicidal toolkit are therefore becoming an alarming problem. Here, we describe our discovery of Nementin, a small molecule that disrupts the nematode nervous system but is ineffective against non-targeted organisms. We find that Nementin also enhances the activity of non-selective pesticides but does so in a nematode-selective manner. Hence, Nementin is an innovative solution to combat parasitic nematodes in a safe and phylum-selective manner. One-Sentence SummaryA C. elegans-based screening pipeline identifies a selective nematicide that also potentiates acetylcholinesterase inhibitors.

pharmacology and toxicology↗

bioRxiv2019

A database for ITS2 sequences from nematodes

Marker gene surveys have a wide variety of applications in species identification, population genetics, and molecular epidemiology. As these methods expand to new types of organisms and additional markers beyond 16S and 18S rRNA genes, comprehensive databases are a critical requirement for proper analysis of these data. Here we present an ITS2 rDNA database for maker gene surveys of both free-living and parasitic nematode populations and the software used to build the database. This is an important resource for researchers working on nematodes and also provides a tool to create ITS2 databases for any given taxonomy.\n\nAvailability and ImplementationThe database is available as an interactive web app at https://cooperia.chgi.ucalgary.ca/Nematode_ITS2/. The full database can also be downloaded from zenodo https://doi.org/10.5281/zenodo.3235802, and the open source software used to create the database, markerDB is available at https://github.com/ucvm/markerDB/releases/latest.

bioinformatics↗

bioRxiv2019

Evidence for the F200Y (TAC) mutation conferring benzimidazole resistance in a southern USA cattle population of Haemonchus placei spreading from a single emergence

The benzimidazoles are one of the most important broad-spectrum anthelmintic drug classes for the control of parasitic nematodes of domestic animals and humans. They have been widely used in the livestock sector, particularly in small ruminants for over 40 years. This has resulted in the development and wide spread of resistance in small ruminant gastrointestinal nematode parasite species, including Haemonchus contortus. Recently, resistance to benzimidazole drugs has been reported in Haemonchus placei, but there is relatively little information on its prevalence. It is important to develop a molecular tools to identify resistance mutations in H. placei early in their development in order to understand the emergence and spread. Our previous study demonstrated the F200Y (TAC) mutation at their early stage in 6/9 H. placei populations derived from southern USA, albeit at low frequencies between 2 and 10%. The present study analysis the phylogenetics of the isotype-1 {beta}-tubulin locus to suggest that F200Y (TAC) mutation has been spread from a single emergence in H. placei; likely by the anthroprogenic movement of ruminant livestock in southern USA. Population genetic data of H. placei using a panel of microsatellite markers revealed little genetic sub-structure, consistent with a high level of gene flow in this region. Overall, these results provide clear genetic evidence for the spread of F200Y (TAC) benzimidazoles resistance mutation to multiple different locations from a single emergence in H. placei.

molecular biology↗