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Vol. 14, Issue 6, 2314-2326, June 2003

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

Lena Hwang ^*, Davina Hocking-Murray , Adam K. Bahrami  , Margareta Andersson , Jasper Rine ^*, and Anita Sil  

^* Department of Molecular and Cellular Biology, University of California Berkeley, Berkeley, California 94720; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California 94143-0414

Submitted January 20, 2002; Revised February 13, 2003; Accepted February 19, 2003
Monitoring Editor: Tim Stearns

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.

Present address: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138.

Corresponding author. E-mail address: sil{at}cgl.ucsf.edu.

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