{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:37:32Z","timestamp":1789529852198,"version":"build-2803163510"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hypoxia is an environmental stress encountered by\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            during invasive pulmonary aspergillosis (IPA). The ability of this mold to adapt to hypoxia is important for fungal virulence and genetically regulated in part by the sterol regulatory element binding protein (SREBP) SrbA. SrbA is required for fungal growth in the murine lung and to ultimately cause lethal disease in murine models of IPA. Here we identified and partially characterized four genes (\n            <jats:italic>dscA<\/jats:italic>\n            ,\n            <jats:italic>dscB<\/jats:italic>\n            ,\n            <jats:italic>dscC<\/jats:italic>\n            , and\n            <jats:italic>dscD<\/jats:italic>\n            , here referred to as\n            <jats:italic>dscA-D<\/jats:italic>\n            ) with previously unknown functions in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            that are orthologs of the\n            <jats:named-content content-type=\"genus-species\">Schizosaccharomyces pombe<\/jats:named-content>\n            genes\n            <jats:italic>dsc1<\/jats:italic>\n            ,\n            <jats:italic>dsc2<\/jats:italic>\n            ,\n            <jats:italic>dsc3<\/jats:italic>\n            , and\n            <jats:italic>dsc4<\/jats:italic>\n            (\n            <jats:italic>dsc1-4<\/jats:italic>\n            ), which encode a Golgi E3 ligase complex critical for SREBP activation by proteolytic cleavage.\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            null\n            <jats:italic>dscA-D<\/jats:italic>\n            mutants displayed remarkable defects in hypoxic growth and increased susceptibility to triazole antifungal drugs. Consistent with the confirmed role of these genes in\n            <jats:named-content content-type=\"genus-species\">S. pombe<\/jats:named-content>\n            , both \u0394\n            <jats:italic>dscA<\/jats:italic>\n            and \u0394\n            <jats:italic>dscC<\/jats:italic>\n            resulted in reduced cleavage of the SrbA precursor protein in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            . Inoculation of corticosteroid immunosuppressed mice with \u0394\n            <jats:italic>dscA<\/jats:italic>\n            and \u0394\n            <jats:italic>dscC<\/jats:italic>\n            strains revealed that these genes are critical for\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            virulence. Reintroduction of SrbA amino acids 1 to 425, encompassing the N terminus DNA binding domain, into the \u0394\n            <jats:italic>dscA<\/jats:italic>\n            strain was able to partially restore virulence, further supporting a mechanistic link between DscA and SrbA function. Thus, we have shown for the first time the importance of a previously uncharacterized group of genes in\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            that mediate hypoxia adaptation, fungal virulence, and triazole drug susceptibility and that are likely linked to regulation of SrbA function.\n          <\/jats:p>","DOI":"10.1128\/ec.00252-12","type":"journal-article","created":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T05:29:50Z","timestamp":1351315790000},"page":"1557-1567","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Dsc Orthologs Are Required for Hypoxia Adaptation, Triazole Drug Responses, and Fungal Virulence in Aspergillus fumigatus"],"prefix":"10.1128","volume":"11","author":[{"given":"Sven D.","family":"Willger","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Disease, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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