A transcriptomic tale of two worms : Evaluating Caenorhabditis elegans as a model for Parascaris univalens in drug resistance studies

Abstract: Parascaris univalens, an equine roundworm, poses a significant threat to foals, potentially causing lethal intestinal ruptures in high infestations. Infection control relies on a limited arsenal of anthelmintic drugs like ivermectin (IVM). However, widespread resistance exacerbated by frequent treatments in foals, first year, challenges effective management. Research into the genetics of this resistance is vital, yet troubled by the parasite’s complex lifecycle, large size, cultivation issues, incomplete genome, and ethical and financial constraints. The free-living nematode Caenorhabditis elegans, known for its simple lifecycle and well-mapped genome, offers a promising alternative model. This thesis assessed C. elegans as a model for studying anthelmintic resistance (AR) in P. univalens and other ascarids, using transcriptomics and gene co-expression networks to bypass traditional method biases and identify novel genes referred to as “core genes”. The study exposed adult P. univalens and C. elegans to different IVM concentrations, revealing distinct genetic responses. Parascaris univalens showed core genes linked to transcriptional suppression, cell cycle inhibition, ribosomal activation, and cuticle/membrane integrity, while C. elegans exhibited diverse core gene involvement, especially upregulated heat shock proteins. Caenorhabditis elegans had more differentially expressed genes (DEGs) in xenobiotic metabolism, with Cytochrome P450s dominance compared to Short Chain Dehydrogenase/Reductases in P. univalens in Phase I. However, the response of Phase II metabolism genes was similar in both species. In addition, the P. univalens IVM response affected numerous ligand-gated ion channels compared to C. elegans, indicating species-specific differences. Despite no shared orthologous core genes and different IVM response functions, both species engaged similar gene families, highlighting C. elegans as a useful model for P. univalens AR studies. Yet, significant differences underline the necessity for supplementary, targeted research in specific parasitic nematodes, crucial for understanding AR mechanisms and developing more effective control strategies in equines.