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dc.contributor.authorBlatzer, Michael
dc.contributor.authorBarker, Bridget M.
dc.contributor.authorWillger, Sven D.
dc.contributor.authorBeckmann, Nicola
dc.contributor.authorBlosser, Sara J.
dc.contributor.authorCornish, Elizabeth J.
dc.contributor.authorMazurie, Aurelien J.
dc.contributor.authorGrahl, Nora
dc.contributor.authorHaas, Hubertus
dc.contributor.authorCramer, Robert A.
dc.date.accessioned2019-04-17T20:57:17Z
dc.date.available2019-04-17T20:57:17Z
dc.date.issued2011-12
dc.identifier.citationBlatzer, Michael, Bridget M. Barker, Sven D. Willger, Nicola Beckmann, Sara J. Blosser, Elizabeth J. Cornish, Aurelien J. Mazurie, Nora Grahl, Hubertus Haas, and Robert A. Cramer. “SREBP Coordinates Iron and Ergosterol Homeostasis to Mediate Triazole Drug and Hypoxia Responses in the Human Fungal Pathogen Aspergillus Fumigatus.” PLoS Genetics 7, no. 12 (December 1, 2011): e1002374. doi:10.1371/journal.pgen.1002374.en_US
dc.identifier.issn1553-7404
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15444
dc.description.abstractSterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance of SREBPs in human health, SREBPs in the human fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. To date, the exact mechanism(s) behind the role of SREBP in these observed phenotypes is not clear. Here, we report that A. fumigatus SREBP, SrbA, mediates regulation of iron acquisition in response to hypoxia and low iron conditions. To further define SrbA's role in iron acquisition in relation to previously studied fungal regulators of iron metabolism, SreA and HapX, a series of mutants were generated in the ΔsrbA background. These data suggest that SrbA is activated independently of SreA and HapX in response to iron limitation, but that HapX mRNA induction is partially dependent on SrbA. Intriguingly, exogenous addition of high iron or genetic deletion of sreA in the ΔsrbA background was able to partially rescue the hypoxia growth, triazole drug susceptibility, and decrease in ergosterol content phenotypes of ΔsrbA. Thus, we conclude that the fungal SREBP, SrbA, is critical for coordinating genes involved in iron acquisition and ergosterol biosynthesis under hypoxia and low iron conditions found at sites of human fungal infections. These results support a role for SREBP–mediated iron regulation in fungal virulence, and they lay a foundation for further exploration of SREBP's role in iron homeostasis in other eukaryotes.en_US
dc.description.sponsorshipAustrian Science Foundation grants FWF P18606-B11, FWF P21643-B11; National Institute of Health grant RR020185; NIH/NIAID grant R01AI81838; Montana State University Agricultural Experiment Stationen_US
dc.language.isoenen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleSREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatusen_US
dc.typeArticleen_US
mus.citation.issue12en_US
mus.citation.journaltitlePLoS Geneticsen_US
mus.citation.volume7en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.pgen.1002374en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.data.thumbpage10en_US
mus.contributor.orcidWillger, Sven D.|0000-0002-9736-2926en_US
mus.contributor.orcidCramer, Robert A.|0000-0001-5503-5006en_US


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CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.
Except where otherwise noted, this item's license is described as CC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.

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