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. (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.
R. Ghosh, E. C. Andersen, J. A. Shapiro, J. P. Gerke, L. Kruglyak, Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans. Science 335, 574–578 (2012). [Abstract] [Full Text]