酿酒酵母的抗真菌活性由钙信号调节。
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Edlind T, Smith L, Henry K, Katiyar S, nickel J
酿酒酵母的抗真菌活性由钙信号调节。
Mol Microbiol, 2002 10月;46(1):257-68。
- PubMed ID
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12366848 (PubMed视图］
- 摘要
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最重要的一类抗真菌药物是唑类(如咪康唑)，它通过抑制固醇生物合成途径中的羊毛甾醇去甲基酶起作用。唑的活性可以通过改变羊毛甾醇去甲基酶的结构、改变其基因ERG11的表达、改变其他甾醇生物合成酶或改变多药转运体的表达来调控。我们提出的证据表明，与酿酒酵母相比，唑的活性也由Ca2+调控的信号调节。(i) Ca2+的加入降低了唑的活性。相反，添加Ca2+螯合剂EGTA可增强唑类活性。(ii) Ca2+结合调节蛋白钙调蛋白的三种结构不同的抑制剂(氟非那嗪、钙咪唑唑和W-7类似物)增强了唑活性。(iii)两种结构不同的Ca2+钙调素调节磷酸酶钙调神经磷酸酶抑制剂(环孢素和FK506)增强了唑类活性。(iv)钙调蛋白Ca2+结合位点被消除的菌株和钙调神经磷酸酶亚单位基因被破坏的菌株表现出增强的唑敏感性;相反，具有组成型激活钙调磷酸酶的突变体表现出对唑的敏感性降低。(v) CRZ1/TCN1编码钙调神经磷酸酶调控的转录因子; 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.