Hwang Lena, Hocking-Murray Davina, Bahrami Adam K, Andersson Margareta, Rine Jasper, Sil Anita
Department of Molecular and Cellular Biology, University of California Berkeley, 94720, USA.
Mol Biol Cell. 2003 Jun;14(6):2314-26. doi: 10.1091/mbc.e03-01-0027. Epub 2003 Mar 20.
A fundamental feature of the fungal pathogen Histoplasma capsulatum is its ability to shift from a mycelial phase in the soil to a yeast phase in its human host. Each form plays a critical role in infection and disease, but little is understood about how these two morphologic phases are established and maintained. To identify phase-regulated genes of H. capsulatum, we carried out expression analyses by using a genomic shotgun microarray representing approximately one-third of the genome, and identified 500 clones that were differentially expressed. Genes induced in the mycelial phase included several involved in conidiation, cell polarity, and melanin production in other organisms. Genes induced in the yeast phase included several involved in sulfur metabolism, extending previous observations that sulfur metabolism influences morphology in H. capsulatum. Other genes with increased expression in the yeast phase were implicated in nutrient acquisition and cell cycle regulation. Unexpectedly, differential regulation of the site of transcript initiation was also observed in the two phases. These findings identify genes that may determine some of the major characteristics of the mycelial and yeast phases.
真菌病原体荚膜组织胞浆菌的一个基本特征是其能够从土壤中的菌丝体阶段转变为人类宿主体内的酵母阶段。每种形态在感染和疾病中都起着关键作用，但对于这两个形态阶段是如何建立和维持的，人们了解甚少。为了鉴定荚膜组织胞浆菌的阶段调控基因，我们使用了一个代表约三分之一基因组的基因组鸟枪法微阵列进行表达分析，并鉴定出500个差异表达的克隆。在菌丝体阶段诱导表达的基因包括一些在其他生物体中参与分生孢子形成、细胞极性和黑色素产生的基因。在酵母阶段诱导表达的基因包括一些参与硫代谢的基因，这扩展了之前关于硫代谢影响荚膜组织胞浆菌形态的观察结果。在酵母阶段表达增加的其他基因与营养获取和细胞周期调控有关。出乎意料的是，在两个阶段还观察到转录起始位点的差异调控。这些发现确定了可能决定菌丝体和酵母阶段一些主要特征的基因。
