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首页> 外文期刊>Archives of microbiology >Validation of Cdc68p as a novel antifungal target
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Validation of Cdc68p as a novel antifungal target

机译：Cdc68p作为新型抗真菌靶标的验证

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Candida albicans is the main cause of systemic fungal infections for which there is an urgent need for novel antifungal drugs. The CP (Cdc68p-Pob3p) complex, which is involved in transcription elongation, was evaluated as a putative antifungal target. In order to predict the consequences of inhibition of this complex, the largest CP subunit in Saccharomyces cerevisiae, Cdc68p, was the first novel target to be tested in GATE, a recently described, quantitative target inactivation system. Depletion of the cell's pool of Cdc68p led to rapid cell death. Subsequently, the C. albicans orthologue of CDC68, CaCDC68, was cloned. Attempts to disrupt both alleles were unsuccessful, thus suggesting an essential role of CaCDC68 in this fungus also. Furthermore, CDC68 was proven to be present in Neurospora crassa and Aspergillus nidulans, thus suggesting that the CP complex is widespread among fungi and could serve as a broad range antifungal target. Analysis of Cdc68p and Pob3p sequences indicated significant structural differences between fungal CP complexes and those present in higher eukaryotes. These results predict that, in principle, fungal-specific ligands of CP complexes could be identified that could subsequently serve as chemical starting points towards the development of new antifungal therapeutic agents. [References: 26]
机译：白色念珠菌是全身性真菌感染的主要原因，因此迫切需要新型抗真菌药物。参与转录延伸的CP（Cdc68p-Pob3p）复合物被评估为推定的抗真菌靶标。为了预测抑制这种复合物的后果，酿酒酵母中最大的CP亚基Cdc68p是在最近描述的定量靶失活系统GATE中测试的第一个新靶标。 Cdc68p细胞池的耗尽导致细胞快速死亡。随后，克隆了CDC68的白色念珠菌直系同源物CaCDC68。破坏两个等位基因的尝试均未成功，因此表明CaCDC68在该真菌中也起着至关重要的作用。此外，事实证明，CDC68存在于克雷索氏菌和构巢曲霉中，因此表明CP复合物在真菌中广泛分布，可作为广泛的抗真菌靶标。 Cdc68p和Pob3p序列分析表明，真菌CP复合物与高等真核生物中存在的CP复合物之间存在明显的结构差异。这些结果预测，原则上，可以鉴定出CP复合物的真菌特异性配体，这些配体随后可以用作开发新的抗真菌治疗剂的化学起点。 [参考：26]

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