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dc.contributor.authorKim, Kwang-Hyung
dc.contributor.authorWillger, Sven D.
dc.contributor.authorPark, Sang-Wook
dc.contributor.authorPuttikamonkul, Srisombat
dc.contributor.authorGrahl, Nora
dc.contributor.authorCho, Yangrae
dc.contributor.authorMukhopadhyay, Biswarup
dc.contributor.authorCramer, Robert A.
dc.contributor.authorLawrence, Christopher B.
dc.date.accessioned2019-04-16T14:35:22Z
dc.date.available2019-04-16T14:35:22Z
dc.date.issued2009-11
dc.identifier.citationKim, Kwang-Hyung, Sven D. Willger, Sang-Wook Park, Srisombat Puttikamonkul, Nora Grahl, Yangrae Cho, Biswarup Mukhopadhyay, Robert A. Cramer, and Christopher B. Lawrence. “TmpL, a Transmembrane Protein Required for Intracellular Redox Homeostasis and Virulence in a Plant and an Animal Fungal Pathogen.” Edited by Barbara Jane Howlett. PLoS Pathogens 5, no. 11 (November 6, 2009): e1000653. doi:10.1371/journal.ppat.1000653.en_US
dc.identifier.issn1553-7366
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15430
dc.description.abstractThe regulation of intracellular levels of reactive oxygen species (ROS) is critical for developmental differentiation and virulence of many pathogenic fungi. In this report we demonstrate that a novel transmembrane protein, TmpL, is necessary for regulation of intracellular ROS levels and tolerance to external ROS, and is required for infection of plants by the necrotroph Alternaria brassicicola and for infection of mammals by the human pathogen Aspergillus fumigatus. In both fungi, tmpL encodes a predicted hybrid membrane protein containing an AMP-binding domain, six putative transmembrane domains, and an experimentally-validated FAD/NAD(P)-binding domain. Localization and gene expression analyses in A. brassicicola indicated that TmpL is associated with the Woronin body, a specialized peroxisome, and strongly expressed during conidiation and initial invasive growth in planta. A. brassicicola and A. fumigatus DtmpL strains exhibited abnormal conidiogenesis, accelerated aging, enhanced oxidative burst during conidiation, and hypersensitivity to oxidative stress when compared to wild-type or reconstituted strains. Moreover, A. brassicicola DtmpL strains, although capable of initial penetration, exhibited dramatically reduced invasive growth on Brassicas and Arabidopsis. Similarly, an A. fumigatus DtmpL mutant was dramatically less virulent than the wild-type and reconstituted strains in a murine model of invasive aspergillosis. Constitutive expression of the A. brassicicola yap1 ortholog in an A. brassicicola DtmpL strain resulted in high expression levels of genes associated with oxidative stress tolerance. Overexpression of yap1 in the DtmpL background complemented the majority of observed developmental phenotypic changes and partially restored virulence on plants. Yap1-GFP fusion strains utilizing the native yap1 promoter exhibited constitutive nuclear localization in the A. brassicicola DtmpL background. Collectively, we have discovered a novel protein involved in the virulence of both plant and animal fungal pathogens. Our results strongly suggest that dysregulation of oxidative stress homeostasis in the absence of TmpL is the underpinning cause of the developmental and virulence defects observed in these studies.en_US
dc.description.sponsorshipNCRR COBRE grant RR020185-01; Royal Thai government mycology scholarship; Virginia Bioinformatics Institute and National Science Foundation award number DBI-044399; USDA Cooperative State Research, Education and Extension Service National Research Initiative grant number #2004-35600-15030en_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.titleTmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogenen_US
dc.typeArticleen_US
mus.citation.issue11en_US
mus.citation.journaltitlePLOS Pathogensen_US
mus.citation.volume5en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1371/journal.ppat.1000653en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.departmentAnimal & Range Sciences.en_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


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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.