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Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in


Blastomyces dermatitidis belongs to a group of human pathogenic fungi that convert between two forms, mold and yeast, in response to temperature. Growth as yeast (37°C) in tissue facilitates immune evasion, whereas growth as mold (22°C) promotes environmental survival, sexual reproduction, and generation of transmissible spores. Despite the importance of dimorphism, how fungi regulate temperature adaptation is poorly understood. We identified SREB, a transcription factor that regulates disparate processes including dimorphism. SREB null mutants, which lack SREB, fail to fully complete the conversion to mold at 22°C. The goal of our research was to characterize how SREB regulates transcription during the switch to mold. Gene expression microarray along with chromatin binding and biochemical analyses indicated that SREB affected several processes including iron homeostasis, lipid biosynthesis, and lipid droplet formation. In vivo, SREB directly bound and regulated genes involved with iron uptake, lipid biosynthesis, and transcription. Functional analysis suggested that lipid metabolism may influence filamentous growth at 22°C. In addition, SREB interacted with another transcription factor, HAPX.


Vyšlo v časopise: Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004959
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004959

Souhrn

Blastomyces dermatitidis belongs to a group of human pathogenic fungi that convert between two forms, mold and yeast, in response to temperature. Growth as yeast (37°C) in tissue facilitates immune evasion, whereas growth as mold (22°C) promotes environmental survival, sexual reproduction, and generation of transmissible spores. Despite the importance of dimorphism, how fungi regulate temperature adaptation is poorly understood. We identified SREB, a transcription factor that regulates disparate processes including dimorphism. SREB null mutants, which lack SREB, fail to fully complete the conversion to mold at 22°C. The goal of our research was to characterize how SREB regulates transcription during the switch to mold. Gene expression microarray along with chromatin binding and biochemical analyses indicated that SREB affected several processes including iron homeostasis, lipid biosynthesis, and lipid droplet formation. In vivo, SREB directly bound and regulated genes involved with iron uptake, lipid biosynthesis, and transcription. Functional analysis suggested that lipid metabolism may influence filamentous growth at 22°C. In addition, SREB interacted with another transcription factor, HAPX.


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