In 2016, nearly 800 million tablets of ivermectin were distributed to countries for use in elimination programs for human filarial diseases. Despite its widespread use, the mode of action of ivermectin against filarial nematodes is not well understood, and its in vivo potency cannot be replicated in vitro. To better understand how ivermectin affects filarial worms, our lab previously performed a transcriptomics study to identify differently expressed genes (DEG) in B. malayi adults and microfilariae after treatment of infected gerbils. This identified 44 DEG that also had C. elegans orthologs available as mutant strains through the C. elegans Genetics Center. In this study, we have assayed these mutant strains for differential sensitivity to ivermectin by measuring three phenotypes affected by ivermectin: egg production, development, and motility. We have identified several resistant and hypersensitive strains of C. elegans as well as differences between responses to the three assays. Mutations conferring resistance included those in
aff-1(
tm2214), a gene involved in cell fusion events in L4 larvae, and
che-12(
e1812), a gene involved in chemotaxis, cilium assembly, and hyperosmotic response. Hypersensitive strains included RB2287 (
lips-7), which is predicted to have deficient lipid hydrolase activity. BC177 (
unc-22) was resistant in both the egg laying and motility assays, but hypersensitive in the development assay. Strikingly, mutations in several genes affecting muscle function caused changes in susceptibility in the motility assay; expression of all these genes was only altered in drug-treated adult male parasites. Overall, at least 18 genes have been identified as altering ivermectin sensitivity in at least one assay, supporting the validity of the overall approach. To test whether these give any insight into how ivermectin acts against filarial parasites, we will examine the effect of RNAi for these genes on ivermectin sensitivity of B. malayi.