Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus

Abstract

Resistance to anthelmintics such as ivermectin (IVM) is currently a major problem in the treatment of Haemonchus contortus, an important parasitic nematode of small ruminants. Although many advances have been made in understanding the IVM resistance mechanism, its exact mechanism remains unclear for H. contortus. Therefore, understanding the resistance mechanism becomes increasingly important for controlling haemonchosis. Recent research showed that the metabolic state of bacteria influences their susceptibility to antibiotics. However, little information is available on the roles of metabolites and metabolic pathways in IVM resistance of H. contortus. In this study, comparative analyses of the metabolomics of IVM-susceptible and -resistant adult H. contortus worms were carried out to explore the role of H. contortus metabolism in IVM resistance. In total, 705 metabolites belonging to 42 categories were detected, and 86 differential metabolites (17 upregulated and 69 downregulated) were identified in the IVM-resistant strain compared to the susceptible one. A KEGG pathway analysis showed that these 86 differential metabolites were enriched in 42 pathways that mainly included purine metabolism; the biosynthesis of amino acids; glycine, serine, and threonine metabolism; and cysteine and methionine metabolism. These results showed that amino acid metabolism may be mediated by the uptake of IVM and related with IVM resistance in H. contortus. This study contributes to our understanding of the mechanisms of IVM resistance and may provide effective approaches to manage infection by resistant strains of H. contortus.