TmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogen

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dc.contributorVirginia Techen
dc.contributor.authorKim, Kwang-Hyunen
dc.contributor.authorWillger, Sven D.en
dc.contributor.authorPark, Sang-Wooken
dc.contributor.authorPuttikamonkul, Srisombaten
dc.contributor.authorGrahl, Noraen
dc.contributor.authorCho, Yangraeen
dc.contributor.authorMukhopadhyay, Biswarupen
dc.contributor.authorCramer, Robert A. Jr.en
dc.date.accessed2014-05-02en
dc.date.accessioned2014-06-17T20:12:10Zen
dc.date.available2014-06-17T20:12:10Zen
dc.date.issued2009-11-06en
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 ΔtmpL 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 ΔtmpL strains, although capable of initial penetration, exhibited dramatically reduced invasive growth on Brassicas and Arabidopsis. Similarly, an A. fumigatus ΔtmpL 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 ΔtmpL strain resulted in high expression levels of genes associated with oxidative stress tolerance. Overexpression of yap1 in the ΔtmpL 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 ΔtmpL 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
dc.description.sponsorshipRAC is currently supported by NCRR COBRE grant RR020185-01. SP is currently supported by a mycology scholarship from the Royal Thai government. CBL is currently supported by the Virginia Bioinformatics Institute and National Science Foundation award number DBI-0443991 and an award from the National Research Initiative of The USDA Cooperative State Research, Education and Extension Service, grant number #2004-35600-15030. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationKim K-H, Willger SD, Park S-W, Puttikamonkul S, Grahl N, et al. (2009) TmpL, a Transmembrane Protein Required for Intracellular Redox Homeostasis and Virulence in a Plant and an Animal Fungal Pathogen. PLoS Pathog 5(11): e1000653. doi:10.1371/journal.ppat.1000653en
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1000653en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/10919/49008en
dc.identifier.urlhttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000653en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAspergillus fumigatusen
dc.subjectFungal geneticsen
dc.subjectFungal pathogensen
dc.subjectfungien
dc.subjectOxidative stressen
dc.subjectPlant fungal pathogensen
dc.subjectPolymerase chain reactionen
dc.subjectRice blast fungusen
dc.titleTmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogenen
dc.title.serialPLoS Pathogensen
dc.typeArticle - Refereeden

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