Comparative analysis on transcriptomics of ivermectin resistant and susceptible strains of Haemonchus contortus

Abstract

Background Ivermectin (IVM) is one of the most important and widely used anthelmintics in veterinary medicine. However, its efficacy is increasingly compromised by widespread resistance, and the exact mechanism of IVM resistance remains unclear for most parasitic nematodes, including Haemonchus contortus, a blood-sucking parasitic nematode of small ruminants. Methods In this study, an H. contortus IVM-resistant strain from Zhaosu, Xinjiang, China, was isolated and assessed by the control test, faecal egg count reduction test (FECRT) and the larval development assay (LDA). Subsequently, comparative analyses on the transcriptomics of IVM-susceptible and IVM-resistant adult worms of this parasite were carried out using RNA sequencing (RNA-seq) and bioinformatics. Results In total, 543 (416 known, 127 novel) and 359 (309 known, 50 novel) differentially expressed genes (DEGs) were identified in male and female adult worms of the resistant strain compared with those of the susceptible strain, respectively. In addition to several previously known candidate genes which were supposed to be associated with IVM resistance and whose functions were involved in receptor activity, transport, and detoxification, we found some new potential target genes, including those related to lipid metabolism, structural constituent of cuticle, and important pathways such as antigen processing and presentation, lysosome, autophagy, apoptosis, and NOD1-like receptor signalling pathways. Finally, the results of quantitative real-time polymerase chain reaction confirmed that the transcriptional profiles of selected DEGs (male: 8 genes, female: 10 genes) were consistent with those obtained by the RNA-seq. Conclusions Our results indicate that IVM has multiple effects, including both neuromuscular and non-neuromuscular targets, and provide valuable information for further studies on the IVM resistance mechanism in H. contortus. Graphical Abstract

Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms

“…Finally, the CC terms displayed the presence of intracellular structures and an intracellular membrane-bounded organelle (GO:0043231) and were also integral components of the cell membrane (GO:0016020, 0016021). These terms play important roles in the parasite development and in the metabolism of anthelmintic drugs [ 50 , 58 ].…”

“…Other important genes, such as those associated with the serine protease family (GO:0008236, GO:0004177), appear to be important as potential vaccine candidates, as has been notified from the nematode Brugia malayi (i.e., Bm-ALT and Bm-VAL-1) [ 63 ]. With these examples, a database of novel transcriptomes could expand our knowledge about nematode biology through the functional annotation of genes and could be directed to obtain future vaccines, molecular targets for competitive studies to inhibit AR receptors and molecular markers for AR diagnosis [ 23 , 50 , 58 ].…”

Caprine Roundworm Nematode Resistance to Macrocyclic Lactones in Northeastern Thailand

“…Moreover, farmers generally used single anthelmintic drugs for their adult animals; some roundworm populations may develop genetic mutations that allow them to resist the effects of these drugs. When this happens, the roundworms are said to be "resistant" to the drugs (Gilleard, 2013;Tuersong et al, 2022). The study of Paraud et al (2016) has similarly shown that when roundworms develop resistance to ivermectin, they may also become resistant to other ML drugs, such as moxidectin.…”