Davis-Hanna Amber, Piispanen Amy E, Stateva Lubomira I, Hogan Deborah A
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Mol Microbiol. 2008 Jan;67(1):47-62. doi: 10.1111/j.1365-2958.2007.06013.x.
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.
经由Ras1 - cAMP - Efg1信号级联反应刺激产生的白色念珠菌菌丝形成，会受到法尼醇（一种白色念珠菌自调节因子）以及月桂醇等小分子的抑制。在含有法尼醇或月桂醇的培养物中，添加二丁酰 - cAMP后菌丝形成得以恢复。携带Ras1显性活性变体且在无诱导刺激时形成菌丝的CAI4 - Ras1(G13V)菌株，在含有法尼醇或月桂醇的培养基中呈酵母样生长；这些化合物还抑制了CAI4 - Ras1(G13V)菌株的热休克敏感性。法尼醇或月桂醇抑制菌丝生长并不需要Pde1或Pde2。Ras1或Cdc35突变后水平升高的两个转录本CTA1和HSP12，在含有法尼醇或月桂醇的培养基中生长的细胞中丰度增加。对携带CTA1和HWP1启动子融合体的菌株在中等浓度法尼醇或月桂醇中生长情况的显微镜分析表明，cAMP抑制基因表达增加的细胞与菌丝形成受抑制的细胞之间存在联系。由于法尼醇和月桂醇会影响多个cAMP控制的输出，我们的研究结果表明，这些化合物影响Ras1 - Cdc35途径的活性，从而导致白色念珠菌形态发生改变。
