| 论文题目: | De-repression of CSP-1 activates adaptive responses to antifungal azoles |
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| 作者: | Chen Xi, Xue Wei, Zhou Jun, Zhang Zhenying, Wei Shiping, Liu Xingyu, Sun Xianyun, Wang Wenzhao, and Li Shaojie*. |
| 联系作者: | |
| 刊物名称: | Sci Rep |
| 期: | |
| 卷: | 6 |
| 页: | 19447 |
| 年份: | 2016 |
| 影响因子: | 5.597 |
| 论文下载: | 下载地址 |
| 摘要: | Antifungal azoles are the major drugs that are used to treat fungal infections. This study found that in response to antifungal azole stress, Neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (CSP-1), a global transcription repressor, at azole-responsive genes. The expression of csp-1 was directly activated by the transcription factors WC-1 and WC-2. Upon ketoconazole (KTC) stress, the transcript levels of wc-1 and wc-2 were not changed, but csp-1 transcription rapidly declined. A chromatin immunoprecipitation-quantitative polymerase chain reaction analysis revealed a rapid reduction in the WC-2 enrichment at the csp-1 promoter upon KTC treatment, which might be responsible for the KTC-induced csp-1 downregulation. Deletion of csp-1 increased resistance to KTC and voriconazole, while csp-1 overexpression increased KTC susceptibility. CSP-1 transcriptionally repressed a number of azole-responsive genes, including genes encoding the azole target ERG11, the azole efflux pump CDR4, and the sterol C-22 desaturase ERG5. Deletion of csp-1 also reduced the KTC-induced accumulation of ergosterol intermediates, eburicol, and 14alpha-methyl-3,6-diol. CSP-1 orthologs are widely present in filamentous fungi, and an Aspergillus fumigatus mutant in which the csp-1 was deleted was resistant to itraconazole. |
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