The use of natural genetic variation in Caenorhabditis elegans to identify novel polymorphisms that can confer benzimidazole resistance in nematodes

Abstract

Benzimidazoles are important drugs for parasite control. Benzimidazole resistance is widespread in parasites of domestic animals, and an emerging problem in human parasites. Caenorhabditis elegans is a powerful model system to study biology of drug resistance. Using natural genetic variation in wild populations of the non-parasitic nematode C. elegans, three novel amino acid substitutions and a deletion in the β-tubulin drug target have been identified that confer varying levels of benzimidazole resistance. These residues are different to those previously reported in other organisms including nematode parasites or fungi and provide new candidate polymorphisms to be investigated in parasitic nematode species including human parasites where resistance is poorly understood. They may also represent new residues important for drug binding. In addition, presence of these resistance conferring polymorphisms in wild populations of a free-living nematode may indicate benzimidazole drug residues in the environment having a significant impact on natural fauna. Finally, the presence of null ben-1 β-tubulin alleles in wild C. elegans populations indicates the functional redundancy of this gene in nature.