Autophagy induced by monensin serves as a mechanism for programmed death in Eimeria tenella

文献类型： 外文期刊

第一作者： Qi, Nanshan

作者： Qi, Nanshan;Liao, Shenquan;Mohiuddin, Mudassar;Li, Juan;Wu, Caiyan;Lv, Minna;Lin, Xuhui;Hu, Junjing;Cai, Haiming;Yu, Linzeng;Xiao, Wenwan;Sun, Mingfei;Qi, Nanshan;Liao, Shenquan;Mohiuddin, Mudassar;Li, Juan;Wu, Caiyan;Lv, Minna;Lin, Xuhui;Hu, Junjing;Cai, Haiming;Yu, Linzeng;Xiao, Wenwan;Sun, Mingfei;Abuzeid, Asmaa M. I.;Li, Guoqing

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关键词： Monensin; Eimeria tenella; Autophagy; Drug resistance

期刊名称：VETERINARY PARASITOLOGY （ 影响因子：2.738； 五年影响因子：2.951 ）

ISSN： 0304-4017

年卷期： 2020 年 287 卷

页码：

收录情况： SCI

摘要： Monensin (Mon), the first ionophoric antibiotic has widely been used for the treatment and prevention of coccidiosis in poultry until recently, however, at present; its efficacy has been compromised with the emergence of many Mon-resistant strains. Knowledge of the mode of the action of anti-parasitic agents is as important as for other antimicrobials, especially for discovery and long term use of the existing drugs. However, little is known about anti-parasitic drug: monensin's, mechanism of action and physiological alteration in Eimeria tenella. In this study, we explored Mon effects on the viability of Mon-Sensitive GZ (MonS-GZ) and Mon-Resistant GZ (MonR-GZ) Eimeria tenella strains using trypan blue staining and investigated Mon-induced autophagy using Western blotting, indirect immunofluorescence assay, and transmission electron microscopy. The results showed that monensin leads to programmed death of E. tenella parasites by inducing autophagy as a mechanism of anticoccidial action. Mon-induced autophagy was indicated by the decreased sporozoites survival rate, ATG8 over expression and localization, and intracellular vacuolar structures and autophagosomes formation in MonS-GZ strain while in MonR-GZ strains autophagy pathway was not triggered. The autophagy inhibitor 3-methyladenine (3-MA) effectively blocked programmed cell death and saved the MonS-GZ sporozoites. These findings indicated that autophagy serves as a potentially important mechanism of E. tenella cell death in response to Mon and disruption of the autophagy pathway may lead to emergence of drug resistance against this anti-parasitic drug.

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