Nguyen Van Q, Sil Anita
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA.
Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4880-5. doi: 10.1073/pnas.0710448105. Epub 2008 Mar 13.
Histoplasma capsulatum, a fungal pathogen of humans, switches from a filamentous spore-forming mold in the soil to a pathogenic budding-yeast form in the human host. This morphologic switch, which is exhibited by H. capsulatum and a group of evolutionarily related fungal pathogens, is regulated by temperature. Using insertional mutagenesis, we identified a gene, RYP1 (required for yeast phase growth), which is required for yeast-form growth at 37 degrees C. ryp1 mutants are constitutively filamentous irrespective of temperature. Ryp1 is a member of a family of fungal proteins that includes Wor1, a master transcriptional regulator of the white-opaque transition required for mating in Candida albicans. Ryp1 associates with its own upstream regulatory region, consistent with a direct role in transcriptional control, and both the protein and its transcript accumulate to high levels in wild-type yeast-phase cells. Microarray analysis demonstrated that Ryp1 is required for the expression of the vast majority of yeast-specific genes, including two genes linked to virulence. Thus, Ryp1 appears to be a critical transcriptional regulator of a temperature-regulated morphologic switch in H. capsulatum.
荚膜组织胞浆菌是一种人类真菌病原体，它能从土壤中的丝状产孢霉菌转变为人类宿主体内的致病性出芽酵母形态。这种形态转变由温度调节，荚膜组织胞浆菌以及一组进化相关的真菌病原体都有此现象。通过插入诱变，我们鉴定出一个基因RYP1（酵母相生长所需基因），它是37摄氏度时酵母形态生长所必需的。ryp1突变体无论温度如何都呈组成型丝状。Ryp1是一类真菌蛋白家族的成员，该家族包括Wor1，Wor1是白色念珠菌交配所需的白色-不透明转变的主要转录调节因子。Ryp1与其自身的上游调控区域结合，这与转录控制中的直接作用一致，并且该蛋白及其转录本在野生型酵母相细胞中积累到高水平。微阵列分析表明，Ryp1是绝大多数酵母特异性基因表达所必需的，包括两个与毒力相关的基因。因此，Ryp1似乎是荚膜组织胞浆菌中温度调节形态转变的关键转录调节因子。
