Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis
Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis
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DOI：
10.1111/j.1365-2958.2007.06013.x
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发表时间：
2008-01-01
影响因子：
3.6
通讯作者：
Hogan, Deborah A.
中科院分区：
文献类型：
--
作者：
Davis-Hanna, Amber;Piispanen, Amy E.;Hogan, Deborah A.
通过Ras 1-cAMP-Efg 1信号级联刺激的白色念珠菌菌丝形成被法尼醇抑制，法尼醇是一种C.白念珠菌自身调节因子和小分子如十二烷醇。在含有法尼醇或十二烷醇的培养物中，在加入二丁酰-cAMP后恢复菌丝形成。CAI 4-Ras 1（G13 V）菌株，携带Ras 1的显性活性变体，在没有诱导刺激的情况下形成菌丝，在含有法尼醇或十二烷醇的培养基中作为酵母生长; CAI 4-Ras 1（G13 V）菌株的热休克敏感性也被这些化合物抑制。Pde 1和Pde 2对法尼醇或十二醇抑制菌丝生长都不是必需的。两个成绩单，CTA 1和HSP 12，这是在较高水平的Ras 1或Cdc 35突变后，增加了丰富的细胞生长与法尼醇或十二烷醇。显微镜分析的菌株携带CTA 1和HWP 1启动子融合生长与中间浓度的法尼醇或十二烷醇表明细胞与cAMP抑制基因的表达增加和抑制菌丝形成的细胞之间的联系。由于几种cAMP控制的输出受到法尼醇和十二烷醇的影响，我们的研究结果表明，这些化合物影响Ras 1-Cdc 35通路的活性，从而导致C.白色念珠菌形态
Candida albicans hypha formation which has been stimulated via the Ras1-cAMP-Efg1 signalling cascade is inhibited by farnesol, a C. albicans autoregulatory factor, and small molecules such as dodecanol. In cultures containing farnesol or dodecanol, hypha formation was restored upon addition of dibutyryl-cAMP. The CAI4-Ras1(G13V) strain, which carries a dominant-active variant of Ras1 and forms hyphae in the absence of inducing stimuli, grew as yeast in medium with farnesol or dodecanol; the heat shock sensitivity of the CAI4-Ras1(G13V) strain was also suppressed by these compounds. Neither Pde1 nor Pde2 was necessary for the repression of hyphal growth by farnesol or dodecanol. Two transcripts, CTA1 and HSP12, which are at higher levels upon mutation of Ras1 or Cdc35, were increased in abundance in cells grown with farnesol or dodecanol. Microscopic analysis of strains carrying CTA1 and HWP1 promoter fusions grown with intermediate concentrations of farnesol or dodecanol indicated a link between cells with the increased expression of cAMP-repressed genes and cells repressed for hypha formation. Because several cAMP-controlled outputs are affected by farnesol and dodecanol, our findings suggest that these compounds impact activity of the Ras1-Cdc35 pathway, thus leading to an alteration of C. albicans morphology.