Selective expression of the virulence factor BAD1 upon morphogenesis to the pathogenic yeast form of Blastomyces dermatitidis: evidence for transcriptional regulation by a conserved mechanism

Most dimorphic fungal pathogens grow as non-pathogenic moulds in soil and c onvert to pathogenic yeast in the host, suggesting that virulence factors a re upregulated during phase transition. Such factors have been difficult to identify. We analysed BAD1 (formerly WI-1), a virulence factor in the dimo rphic fungus Blastomyces dermatitidis, for expression in yeast and mycelial morphotypes. BAD1 was expressed in yeast but not in mycelia of North Ameri can strains of B. dermatitidis, and this expression pattern was confirmed f or BAD1 transcript. BAD1 under the control of its promoter was transferred into African B. dermatitidis lacking a native BAD1 locus, and phase-specifi c expression was conserved. Sequence similarity was identified between the BAD1 promoter and the promoters of two yeast phase-specific genes in Histop lasma capsulatum, In H. capsulatum BAD1 transformants, yeast phase-specific expression of BAD1 was conserved, and no transcript was detected in myceli a. BAD1 beta -galactosidase reporter fusions analysed in a. dermatitidis an d H. capsulatum confirmed that BAD1 is transcriptionally regulated in both fungi. BAD1 promoter activity and surface BAD1 expression were detected 6 h after shifting mycelia to 37 degreesC. Thus, BAD1 is expressed after trans ition to the pathogenic yeast morphotype and is regulated by a mechanism fo r phase-specific gene expression that appears to be conserved.