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法尼醇介导的白色念珠菌酵母生长抑制及二酰基甘油类似物的挽救作用

Farnesol-mediated inhibition of Candida albicans yeast growth and rescue by a diacylglycerol analogue.

作者信息

Uppuluri Priya, Mekala Satish, Chaffin W LaJean

机构信息

Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

出版信息

Yeast. 2007 Aug;24(8):681-93. doi: 10.1002/yea.1501.

Abstract

During Candida albicans yeast cell growth to early stationary phase, metabolites accumulate in the medium, including the quorum-sensing molecule farnesol. We found that besides germ tube inhibition, 40 microM farnesol also inhibited C. albicans yeast growth under yeast growth permissive conditions. Consistent with this observation, transcriptional analysis of yeast cells resuspended in fresh medium with 40 microM farnesol revealed that genes involved in hyphal formation, GTPase activation, mitosis and DNA replication were downregulated many-fold. Farnesol-mediated inhibition of yeast growth was dependent on the growth phase of the C. albicans cells. The growth defect was relieved by addition of a diacylglycerol analogue, implicating phosphatidylinositol signalling in the delay. Although diacylglycerol is an activator of protein kinase C (PKC) in mammalian cells, there is some question about activation of fungal PKCs. A mutant strain deleted for PKC1 responded to farnesol and the diacylglycerol analogue similar to wild-type, suggesting that PKC is not the target of the diacylglycerol analogue.

摘要

在白色念珠菌酵母细胞生长至早期稳定期的过程中,代谢产物会在培养基中积累,包括群体感应分子法尼醇。我们发现,除了抑制芽管形成外,40微摩尔的法尼醇在酵母生长允许的条件下也会抑制白色念珠菌酵母的生长。与此观察结果一致,对悬浮在含有40微摩尔法尼醇的新鲜培养基中的酵母细胞进行转录分析发现,参与菌丝形成、GTP酶激活、有丝分裂和DNA复制的基因被下调了许多倍。法尼醇介导的酵母生长抑制取决于白色念珠菌细胞的生长阶段。添加二酰基甘油类似物可缓解生长缺陷,这表明磷脂酰肌醇信号传导参与了延迟过程。尽管二酰基甘油在哺乳动物细胞中是蛋白激酶C(PKC)的激活剂,但关于真菌PKC的激活存在一些疑问。缺失PKC1的突变菌株对法尼醇和二酰基甘油类似物的反应与野生型相似,这表明PKC不是二酰基甘油类似物的作用靶点。

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