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

Marty AJ, Broman AT, Zarnowski R, Dwyer TG, Bond LM, Lounes-Hadj Sahraoui A, Fontaine J, Ntambi JM, Keleş S, Kendziorski C, Gauthier GM - PLoS Pathog. (2015)

Bottom Line: This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation.Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX.Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.

ABSTRACT
In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

No MeSH data available.


Growth of B. dermatitidis yeast is influenced by exogenous iron.(A)B. dermatitidis yeast were grown in iron deplete and replete liquid HMM at 37°C. (B–D)B. dermatitidis yeast were grown in media supplemented with 1, 5, and 10 μM FeCl3 along with 0–1.0 mM deferiprone (DFP), an iron chelator.
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ppat.1004959.g003: Growth of B. dermatitidis yeast is influenced by exogenous iron.(A)B. dermatitidis yeast were grown in iron deplete and replete liquid HMM at 37°C. (B–D)B. dermatitidis yeast were grown in media supplemented with 1, 5, and 10 μM FeCl3 along with 0–1.0 mM deferiprone (DFP), an iron chelator.

Mentions: The acquisition of iron from the host or the environment is important for growth, and fungi have developed several mechanisms for iron uptake [33]. The influence of iron on the growth of B. dermatitidis is unclear and one study concluded that iron failed to enhance growth of yeast during iron starvation; however, a high concentration of ferric iron was used [34]. To further characterize the effect of iron on B. dermatitidis, yeast were grown under iron-poor media or media containing 3, 5, and 10 μM FeCl3. B. dermatitidis yeast exhibited slow growth under iron-deplete conditions, whereas the addition of 3 μM FeCl3 improved growth (Fig 3A). Treatment of yeast with deferiprone (DFP), an iron chelator, impaired growth in a dose-dependent manner and the degree of growth inhibition was influenced by the concentration of exogenous iron (Fig 3B–3D). Collectively, these findings indicate that the acquisition of iron is important for the growth of B. dermatitidis.


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

Marty AJ, Broman AT, Zarnowski R, Dwyer TG, Bond LM, Lounes-Hadj Sahraoui A, Fontaine J, Ntambi JM, Keleş S, Kendziorski C, Gauthier GM - PLoS Pathog. (2015)

Growth of B. dermatitidis yeast is influenced by exogenous iron.(A)B. dermatitidis yeast were grown in iron deplete and replete liquid HMM at 37°C. (B–D)B. dermatitidis yeast were grown in media supplemented with 1, 5, and 10 μM FeCl3 along with 0–1.0 mM deferiprone (DFP), an iron chelator.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482641&req=5

ppat.1004959.g003: Growth of B. dermatitidis yeast is influenced by exogenous iron.(A)B. dermatitidis yeast were grown in iron deplete and replete liquid HMM at 37°C. (B–D)B. dermatitidis yeast were grown in media supplemented with 1, 5, and 10 μM FeCl3 along with 0–1.0 mM deferiprone (DFP), an iron chelator.
Mentions: The acquisition of iron from the host or the environment is important for growth, and fungi have developed several mechanisms for iron uptake [33]. The influence of iron on the growth of B. dermatitidis is unclear and one study concluded that iron failed to enhance growth of yeast during iron starvation; however, a high concentration of ferric iron was used [34]. To further characterize the effect of iron on B. dermatitidis, yeast were grown under iron-poor media or media containing 3, 5, and 10 μM FeCl3. B. dermatitidis yeast exhibited slow growth under iron-deplete conditions, whereas the addition of 3 μM FeCl3 improved growth (Fig 3A). Treatment of yeast with deferiprone (DFP), an iron chelator, impaired growth in a dose-dependent manner and the degree of growth inhibition was influenced by the concentration of exogenous iron (Fig 3B–3D). Collectively, these findings indicate that the acquisition of iron is important for the growth of B. dermatitidis.

Bottom Line: This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation.Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX.Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.

ABSTRACT
In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

No MeSH data available.