Stead David, Findon Helen, Yin Zhikang, Walker Janet, Selway Laura, Cash Philip, Dujon Bernard A, Hennequin Christophe, Brown Alistair J P, Haynes Ken
COGEME Proteomics Research Facility 1, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, UK.
Proteomics. 2005 May;5(7):1838-48. doi: 10.1002/pmic.200401064.
Inactivation of the gene encoding the transcriptional activator Ace2 in the fungal pathogen Candida glabrata results in an almost 200-fold increase in virulence characterised by acute mortality and a massive over-stimulation of the pro-inflammatory arm of the innate immune system. In this study we have adopted a proteomics approach to identify cellular functions regulated by C. glabrata Ace2 that might contribute to this increase in virulence. A two-dimensional polyacrylamide gel electrophoresis map of the C. glabrata proteome was constructed. We identified a total of 123 proteins, 61 of which displayed reproducible and statistically significant alterations in their levels following inactivation of ACE2. Of these, the levels of 32 proteins were elevated, and 29 were reduced in ace2 cells. These data show that Ace2 influences metabolism, protein synthesis, folding and targeting, and aspects of cell growth and polarisation. Some of these functions are likely to contribute to the effects of Ace2 upon the virulence of C. glabrata.
在真菌病原体光滑念珠菌中，编码转录激活因子Ace2的基因失活会导致毒力增加近200倍，其特征为急性死亡率以及先天性免疫系统促炎分支的大量过度刺激。在本研究中，我们采用蛋白质组学方法来鉴定由光滑念珠菌Ace2调控的可能导致这种毒力增加的细胞功能。构建了光滑念珠菌蛋白质组的二维聚丙烯酰胺凝胶电泳图谱。我们总共鉴定出123种蛋白质，其中61种在ACE2失活后其水平表现出可重复且具有统计学意义的变化。其中，32种蛋白质的水平在ace2细胞中升高，29种降低。这些数据表明Ace2影响代谢、蛋白质合成、折叠和靶向，以及细胞生长和极化的各个方面。其中一些功能可能有助于Ace2对光滑念珠菌毒力产生影响。
