PubMed · 3698556
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G A Sarosi, S F Davies. 1986. Blastomycosis.. https://pubmed.ncbi.nlm.nih.gov/3698556/
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In the present study, we demonstrate that the yeast form of Blastomyces dermatitidis can proliferate for short periods of time in the absence of ferric iron but not in the absence of calcium or magnesium. The results of this study shed light on the resistance of B. dermatitidis to chelating agents, such as deferoxamine, and may explain how B. dermatitidis resists the iron-binding activity of serum transferrin.
Blastomyces dermatitidis is a dimorphic fungal pathogen that converts from mycelia or conidia to a host-adapted yeast morphotype upon infection. Conversion to the yeast form is accompanied by the production of the virulence factor BAD1. Yeast-phase-specific expression of BAD1 is transcriptionally regulated, and its promoter shares homology with that of the yeast-phase-specific gene YPS3 of Histoplasma capsulatum. Serial truncations of the BAD1 upstream region were fused to the lacZ reporter to define functional areas in the promoter. Examination of PBAD1-lacZ fusions in B. dermatitidis indicated that BAD1 transcription is upregulated in the yeast phase. The 63-nucleotide box A region conserved in the YPS3 upstream region was shown to be an essential component of the minimal BAD1 promoter. A matched PYPS3-lacZ construct indicated that this same region was needed for minimal YPS3 promoter activity in B. dermatitidis transformants. Reporter activity in H. capsulatum transformants similarly showed a requirement for box A in the minimal BAD1 promoter. Several putative transcription factor binding sites were identified within box A of BAD1. Replacement of two of these predicted sites within box A--a cAMP responsive element and a Myb binding site--sharply reduced transcriptional activity, indicating that these regions are critical in dictating the yeast-phase-specific expression of this crucial virulence determinant of B. dermatitidis.
Blastomycosis is an endemic mycoses in the central United States caused by a dimorphic fungus, Blastomyces dermatitidis, that exists in nature in mycelial phase and converts to yeast phase at body temperature. The organism may produce epidemics of infection following a point source of infection or sporadic endemic infection. Blastomycosis can be a subclinical illness with subsequent protection against progressive infection afforded by cellular immune mechanisms, but it may present with progressive disease with either pulmonary or extrapulmonary disease or both. Itraconazole has been shown to be the drug of choice for both infections, except in cases of life-threatening infection when amphotericin B should be used.