Clioquinol (CQ) has been used as a classical antimicrobial agent for many years. However, its mode of action is still unclear. In our study, the growth of Candida albicans and Saccharomyces cerevisiae was inhibited by CQ. It did not kill yeast cells, but shortened G1 phase and arrested cell cycle at G2/M phase. By using two-dimensional electrophoresis based proteomic approach, six proteins were found to be significantly affected by CQ. Among them, four (PDC1, ADH1, TDH3, IPP1) were up-regulated and the other two (TDH1 and PGK1) were down-regulated. According to the Saccharomyces Genome Database (SGD), these proteins were involved in various biological processes including glycolytic fermentation, gluconeogenesis, glycolytic process, amino acid catabolism, redox reaction and reactive oxygen species metabolic process. It was noted that there was a link between TDH3 and cell cycle. The overexpression of TDH3 phenocopied CQ treatment and arrested the cell cycle at G2/M phase. RT-PCR analysis showed that the mRNA levels of CLN3 and CDC28, critical genes for passage through G1 phase, were up-regulated after the treatment of CQ as well as the overexpression of TDH3. It demonstrates that CQ inhibits the growth of yeast by up-regulating the expression of TDH3 to influence the cell cycle. It is expected to provide new insights for the antimicrobial mechanism of CQ.

氯喹诺醇（CQ）多年来已被用作经典的抗菌剂。但是，其作用方式仍不清楚。在我们的研究中，CQ抑制了白色念珠菌和酿酒酵母的生长。它没有杀死酵母细胞，但缩短了G1期，并使细胞周期停滞在G2 / M期。通过使用基于二维电泳的蛋白质组学方法，发现六种蛋白质受到CQ的显着影响。其中，四个（PDC1，ADH1，TDH3，IPP1）被上调，另外两个（TDH1和PGK1）被下调。根据酵母菌在基因组数据库（SGD）中，这些蛋白质参与了各种生物过程，包括糖酵解发酵，糖异生，糖酵解过程，氨基酸分解代谢，氧化还原反应和活性氧代谢过程。注意到TDH3和细胞周期之间存在联系。TDH3的表型过度表达CQ处理，并使细胞周期停滞在G2 / M期。RT-PCR分析表明，CQ处理及TDH3过表达后，通过G1期的关键基因CLN3和CDC28的mRNA水平上调。。它表明CQ通过上调TDH3的表达来影响细胞周期来抑制酵母的生长。有望为CQ的抗菌机制提供新的见解。