SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis

Autor: Thomas D. Sullivan, Sergio S. Gallardo, T. Tristan Brandhorst, Christina A. Cuomo, Garret Suen, Bruce S. Klein, Cameron R. Currie, Amber Vanden Wymelenberg, Gregory M. Gauthier
Rok vydání: 2010
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Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 6, Iss 4, p e1000846 (2010)
ISSN: 1553-7374
DOI: 10.1371/journal.ppat.1000846
Popis: Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism. At 22°C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37°C they convert to budding yeast. The ability to switch between these forms is essential for virulence in mammals and may enable these organisms to survive in the soil. To identify genes that regulate this phase transition, we used Agrobacterium tumefaciens to mutagenize B. dermatitidis conidia and screened transformants for defects in morphogenesis. We found that the GATA transcription factor SREB governs multiple fates in B. dermatitidis: phase transition from yeast to mold, cell growth at 22°C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22°C, and are unable to suppress siderophore biosynthesis under iron-replete conditions. The defect in morphogenesis in the SREB mutant was independent of exogenous iron concentration, suggesting that SREB promotes the phase transition by altering the expression of genes that are unrelated to siderophore biosynthesis. Using bioinformatic and gene expression analyses, we identified candidate genes with upstream GATA sites whose expression is altered in the null mutant that may be direct or indirect targets of SREB and promote the phase transition. We conclude that SREB functions as a transcription factor that promotes morphogenesis and regulates siderophore biosynthesis. To our knowledge, this is the first gene identified that promotes the conversion from yeast to mold in the dimorphic fungi, and may shed light on environmental persistence of these pathogens.
Author Summary The dimorphic fungi are the most common cause of invasive fungal disease worldwide. In the soil, these fungi grow as mold that produce infectious spores; when inhaled into the warmer lungs of a mammalian host, the spores convert into yeast, which cause infection. The change in shape between mold and yeast is a crucial event in the lifecycle of these fungi. The molecular regulation of this morphologic switch, or phase transition, is poorly understood. The goal of our research was to identify and characterize novel gene(s) that govern the phase transition in dimorphic fungi using Blastomyces dermatitidis as a model organism. Using insertional mutagenesis, we identified a gene, SREB, which encodes a transcription factor that affects phase transition and regulates the production of iron-gathering molecules or siderophores. When SREB is deleted, B. dermatitidis fails to complete the conversion from yeast to mold, grows poorly at environmental temperature, has yellow-orange colony pigmentation, and cannot properly repress the biosynthesis of siderophores. We also identified two types of siderophores produced by B. dermatitidis. To our knowledge, SREB is the first gene identified that promotes the conversion from yeast to mold, a process important for survival in the environment and generation of infectious spores.
Databáze: OpenAIRE
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