Background

Nitazoxanide is a broad-spectrum, anti-parasitic, anti-protozoal, anti-viral drug, whose mechanisms of action have remained elusive.

Objective

In this study, we aimed to provide insight into the mechanisms of action of nitazoxanide and the related eukaryotic host responses by characterizing transcriptome profiles of Saccharomyces cerevisiae exposed to nitazoxanide.

Methods

RNA-Seq was used to investigate the transcriptome profiles of three strains of S. cerevisiae with dsRNA virus-like elements, including a strain that hosts M28 encoding the toxic protein K28. From the strain with M28, an additional sub-strain was prepared by excluding M28 using a nitazoxanide treatment.

Results

Our transcriptome analysis revealed the effects of nitazoxanide on ribosome biogenesis. Many genes related to the UTP A, UTP B, Mpp10-Imp3-Imp4, and Box C/D snoRNP complexes were differentially regulated by nitazoxanide exposure in all of the four tested strains/sub-strains. Examples of the differentially regulated genes included UTP14, UTP4, NOP4, UTP21, UTP6, and IMP3. The comparison between the M28-laden and non-M28-laden sub-strains showed that the mitotic cell cycle was more significantly affected by nitazoxanide exposure in the non-M28-laden sub-strain.

Conclusions

Overall, our study reveals that nitazoxanide disrupts regulation of ribosome biogenesis-related genes in yeast.

中文翻译：

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抗感染性硝唑尼特破坏酵母中核糖体生物发生相关基因的转录。

背景

硝唑尼特是一种广谱，抗寄生虫，抗原生动物，抗病毒的药物，其作用机理尚不清楚。

目的

在这项研究中，我们旨在通过表征暴露于硝唑尼特的酿酒酵母的转录组谱，来提供硝唑尼特作用机理和相关的真核宿主反应的见解。

方法

RNA-Seq用于研究三株带有dsRNA病毒样元件的酿酒酵母菌株的转录组谱，包括含有编码有毒蛋白K28的M28的菌株。从具有M28的菌株中，通过使用硝唑烷化物处理排除M28，制备了另外的亚菌株。

结果

我们的转录组分析揭示了硝唑尼特对核糖体生物发生的影响。在所有四个测试菌株/亚菌株中，硝唑尼特暴露均与UTPA A，UTPA B，Mpp10-Imp3-Imp4和Box C / D snoRNP复合物有关的许多基因均受到差异调节。差异调节的基因的实例包括UTP14，UTP4，NOP4，UTP21，UTP6，和IMP3。载有M28的亚菌株和未载有M28的亚菌株之间的比较表明，在未载有M28的亚菌株中，硝唑尼特暴露对有丝分裂细胞周期的影响更大。

结论

总体而言，我们的研究表明，硝唑尼特破坏了酵母中核糖体生物发生相关基因的调控。