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Role of autophagy in resistance to ivermectin in Haemonchus contortus

文献类型： 外文期刊

作者： Fu, Nana 1 ; Luo, Xiaoping 3 ; Li, Junyan 3 ; Zhou, Xuezhang 1 ; Du, Jun 1 ; Zhai, Bintao 4 ; Li, Anben 1 ; Yang, Xiaoye 5 ; Liu, Yang 1 ;

作者机构： 1.Ningxia Univ, Sch Life Sci, Yinchuan 750021, Peoples R China

2.Ningxia Univ, Key Lab, Minist Educ Protect & Utilizat Special Biol Resour, Yinchuan 750021, Peoples R China

3.Inner Mongolia Acad Agr & Anim Husb Sci, Hohhot 010030, Peoples R China

4.Chinese Acad Agr Sci, Minist Agr, Lanzhou Inst Husb & Pharmaceut Sci, Key Lab Vet Pharmaceut Dev, Lanzhou 730050, Peoples R China

5.Inner Mongolia Agr Univ, Coll Vet Med, Hohhot 010018, Peoples R China

关键词： Haemonchus contortus; drug resistance; autophagy; ivermectin

期刊名称：VETERINARY PARASITOLOGY （ 影响因子：2.2； 五年影响因子：2.4 ）

ISSN： 0304-4017

年卷期： 2025 年 333 卷

页码：

收录情况： SCI

摘要： Haemonchus contortus is a highly pathogenic gastrointestinal nematode that parasitizes the abomasum of cattle, sheep, and other ruminants. Long-term use of large quantities of ivermectin (IVM) to control H. contortus has resulted in the development of drug resistance. However, the mechanism of IVM resistance in H. contortus remains incompletely understood. Autophagy is involved in regulating drug resistance in some parasites. Previous omics sequencing of differentially expressed genes in drug-resistant strains of H. contortus revealed substantial enrichment of autophagy-related pathway. Therefore, autophagy was used as the entry point in this study to investigate its role in IVM resistance in H. contortus. Larval migration inhibition test, RT-qPCR, and transmission electron microscopy of IVM-susceptible and -resistant strains were performed. Results showed that the H. contortus-resistant strain had higher autophagy levels than the susceptible strain. After IVM treatment, the susceptible strain exhibited significant upregulation of the autophagy-related genes lgg-1, lgg-2, bec-1, lc3, and atg-18 and significant downregulation of the autophagy substrate sqst-1, along with an increased number of autolysosomes. Additionally, the autophagy inhibitor 3-MA reduced the resistance of the IVM-resistant H. contortus strain toward IVM after inhibiting autophagy, and the autophagy inducer urolithin A reduced the susceptibility of the IVM-susceptible H. contortus strain of IVM after activating its autophagy. These results demonstrate that IVM promotes autophagy in H. contortus and that autophagy is involved in regulating drug resistance in H. contortus. This study fills the knowledge gap regarding the role of autophagy in H. contortus drug resistance and provides a novel perspective on the study of drug resistance mechanisms in H. contortus.

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