[
International Worm Meeting,
2019]
Parasitic nematodes are a major burden on livestock and human health around the world. Anthelmintic drugs are the front line to fight these infections, but resistance to the drugs continue to increase worldwide. To fight this resistance, a thorough understanding of the genetics and mechanisms of resistance to all major drug classes are essential, especially for the most commonly used benzimidazole (BZ) class. Three well known BZ resistance variants (F200Y, E198A, F167Y) are found in a beta-tubulin encoding gene in many parasitic nematode species. Additionally, two other resistance variants have been discovered in parasitic and free-living nematode populations at the 198 position, E198V and E198L. Our lab recently identified a number of other alleles segregating at low frequency within the Caenorhabditis elegans beta-tubulin isotype-1 locus that are correlated with BZ resistance. To validate whether any of these alleles underlie resistance to benzimidazoles, we generated genome-edited strains introducing each of the discovered alleles into a defined C. elegans genetic background (N2). Using high-throughput assays of fecundity and growth rate, we quantitatively measured resistance conferred by each of these alleles. In addition, we used tissue-specific promoters driving expression of a susceptible beta-tubulin gene in an otherwise resistant genetic background to test how these alleles affect beta-tubulin function to confer resistance. To the best of our knowledge, we have characterized the resistance profile of all currently identified nematode benzimidazole resistance alleles.