EtcPRSMut as a molecular marker of halofuginone resistance in Eimeria tenella and Toxoplasma gondii

Sun, Pei; Zhang, Yuanyuan; Wang, Chaoyue; Hu, Dandan; Liu, Jie; Chen, Linlin; Shi, Fangyun; Tang, Xinming; Hao, Zhenkai; Suo, Jingxia; Yu, Yonglan; Suo, Xun; Liu, Xianyong

doi:10.1016/j.isci.2023.106334

Cited by 7 publications

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“…However, the therapeutic utility of halofuginone and its analogs have been stymied by resistance, and the previously unknown mode of action in the parasite has impeded the rational development of drugs with improved pharmacological properties ( Peek and Landman, 2003 ). Our recent work has identified that EtcPRS Mut also confers halofuginone resistance in E. tenella ( Sun et al, 2023 ). Here, we performed transcriptome analysis to explore the potential halofuginone resistance mechanism in E. tenella .…”

Section: Discussionmentioning

confidence: 99%

“…The sensitive E. tenella Xinjiang strain used was maintained in the laboratory, which is sensitive to the anticoccidial drug halofuginone and used as the parental line. The resistant strains were generated under halofuginone (30 mg/kg) through an experimental evolution strategy and verified through a drug resistance test ( Sun et al, 2023 ). The procedures for collection, sporulation and purification of the parasite were carried out as the previous report ( Duan et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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Transcriptome profile of halofuginone resistant and sensitive strains of Eimeria tenella

et al. 2023

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The antiparasitic drug halofuginone is important for controlling apicomplexan parasites. However, the occurrence of halofuginone resistance is a major obstacle for it to the treatment of apicomplexan parasites. Current studies have identified the molecular marker and drug resistance mechanisms of halofuginone in Plasmodium falciparum. In this study, we tried to use transcriptomic data to explore resistance mechanisms of halofuginone in apicomplexan parasites of the genus Eimeria (Apicomplexa: Eimeriidae). After halofuginone treatment of E. tenella parasites, transcriptome analysis was performed using samples derived from both resistant and sensitive strains. In the sensitive group, DEGs associated with enzymes were significantly downregulated, whereas the DNA damaging process was upregulated after halofuginone treatment, revealing the mechanism of halofuginone-induced parasite death. In addition, 1,325 differentially expressed genes (DEGs) were detected between halofuginone resistant and sensitive strains, and the DEGs related to translation were significantly downregulated after halofuginone induction. Overall, our results provide a gene expression profile for further studies on the mechanism of halofuginone resistance in E. tenella.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%