Identifying Phase-specific Genes in the Fungal Pathogen Histoplasma capsulatum Using a Genomic Shotgun Microarray□D

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 onethird 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.