4.6 Article

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

期刊

PARASITES & VECTORS
卷 15, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s13071-022-05274-y

关键词

Haemonchus contortus; Ivermectin; Resistance mechanism; Transcriptome analysis

资金

  1. National Natural Science Foundation of China [31872462, 32172881]

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This study identified differentially expressed genes (DEGs) in Ivermectin (IVM)-resistant Haemonchus contortus compared to susceptible strains, providing insights into the molecular mechanisms of IVM resistance. The study revealed potential new target genes related to lipid metabolism, cuticle structure, and important pathways such as antigen processing, lysosome, autophagy, apoptosis, and NOD1-like receptor signaling pathways. These findings contribute to a better understanding of IVM resistance in H. contortus.
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.

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