Anti-infective nitazoxanide disrupts transcription of ribosome biogenesis-related genes in yeast

다국어 초록 (Multilingual Abstract)

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 substrain 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.