Natural Variation in a Chloride Channel Subunit Confers Avermectin Resistance in C. elegans

Abstract

Natural Resistance Avermectins are the most widely used class of anthelmintic drugs, both as pesticides and as treatments for nematode-borne diseases, with the evolution of resistance presenting a major global health and agricultural problem. Ghosh et al. (p. 574 ; see the Perspective by Wolstenholme ) observed resistance to avermectin in the model nematode Caenorhabditis elegans that varies among isolates. This resistance is caused by a naturally occurring four–amino acid deletion in the ligand-binding domain of a glutamate-gated chloride channel. This variant also conferred resistance to the avermectin-producing ubiquitous soil bacterium, Streptomyces zitilis . Many nematodes spend at least part of their life cycle in soil, which may explain avermectin resistance among nematode species.