Gene expression of three ivermectin selected resistant Caenorhabditis elegans strains compared to the susceptible N2 strain

Ivermectin (IVM) is a cornerstone of nematode control. However, its efficacy is increasingly compromised by emerging resistance in targets parasites. Here, we investigated these mechanisms in three independently evolved Caenorhabditis elegans lineages exposed to stepwise ivermectin selection. Remarkably, these populations, although distinct, converged over time to a comparable and stabilized high level of IVM resistance. RNAseq analysis across lineages revealed a conserved enrichment for ciliary/neuronal pathways including genes expressed in amphid/phasmid, indicating remodeling of the chemosensory/ciliary network as resistance intensifies. All resistant lines also converged on the dye-filling defective (Dyf) phenotype that emerged during selection at stages coinciding with sharp gains in ivermectin tolerance, implicating amphid structure/function in the establishment of durable resistance. Our results support a two-phase associative model in which early PGP-mediated tolerance precedes the emergence of ciliary/amphidial signatures and a Dyf phenotype during selection that durably reduces susceptibility. Overall design: RNA-seq profiling of three ivermectin-selected resistant Caenorhabditis elegans strains and of the wild-type N2 strain at the L4 stage