抗真菌活性在酿酒酵母是由钙信号调制的。
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史密斯Edlind T, L,亨利·K Katiyar年代,尼克尔斯J
抗真菌活性在酿酒酵母是由钙信号调制的。
摩尔Microbiol。2002年10月,46 (1):257 - 68。
- PubMed ID
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12366848 (在PubMed]
- 文摘
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最重要组抗真菌唑类(如咪康唑),该法案通过抑制羊毛甾醇demethylase甾醇生物合成途径。氮杂茂活动可以通过结构变化来调制羊毛甾醇demethylase, ERG11基因的表达改变,改变其他甾醇生物合成的酶或耐多药转运蛋白的表达改变。我们目前的证据表明,唑活动与酿酒酵母也由Ca2 +的监管信号调制。(我)唑活动降低了Ca2 +的加法。相反,唑活性增强的Ca2 +螯合剂EGTA。(2)三个结构不同的抑制剂(氟奋乃静,calmidazolium,若模拟)的Ca2 +绑定监管蛋白质钙调蛋白增强唑活动。(3)两种结构不同的抑制剂(环孢菌素和吸收FK506)的Ca2 + -calmodulin-regulated磷酸酶钙调磷酸酶增强唑活动。(iv)菌株的Ca2 +钙调蛋白的结合位点被淘汰和紧张的钙调磷酸酶亚基基因中断了增强唑的敏感性;相反,一个突变体与持续激活钙调磷酸酶磷酸酶证实唑的敏感性下降。(v) CRZ1 / TCN1编码转录因子调控钙调磷酸酶磷酸酶; its disruption enhanced azole sensitivity, whereas its overexpression decreased azole sensitivity. All the above treatments had comparable effects on the activity of terbinafine, an inhibitor of squalene epoxidase within the sterol biosynthesis pathway, but had little or no effect on the activity of drugs with unrelated targets. (vi) Treatment of S. cerevisiae with azole or terbinafine resulted in transcriptional upregulation of genes FKS2 and PMR1 known to be Ca2+ regulated. A model to explain the role of Ca2+-regulated signalling in azole/terbinafine tolerance is proposed.