Publication
Genomic landscape of drug response reveals novel mediators of anthelmintic resistance
Publisher:
Cold Spring Harbor Laboratory
Date:
12-11-2021
DOI:
10.1101/2021.11.12.465712
Abstract: Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to improving the efficacy and sustainability of parasite control. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor, cky-1 , in ivermectin resistance. This gene is within a locus under selection in ivermectin resistant populations worldwide functional validation using knockout experiments supports a role for cky-1 overexpression in ivermectin resistance. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode, and identifies variants for the development of molecular diagnostics to combat drug resistance in the field. Genetic mapping of known and novel anthelmintic resistance-associated alleles in a multi-drug resistant parasitic nematode