{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:01:16Z","timestamp":1790074876329,"version":"4.0.1"},"reference-count":51,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373493"],"award-info":[{"award-number":["82373493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015746","name":"Large-Scale Instrument and Equipment Sharing Foundation of Wuhan University","doi-asserted-by":"publisher","award":["2026-53"],"award-info":[{"award-number":["2026-53"]}],"id":[{"id":"10.13039\/501100015746","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The WOPR family of transcription factors regulates morphological transitions and virulence in diverse fungal pathogens, yet their roles in\n                      <jats:italic toggle=\"yes\">Nakaseomyces glabratus<\/jats:italic>\n                      \u2014the second leading cause of candidiasis\u2014remain uncharacterized. Through homology searches, we identified two WOPR domain-containing proteins in\n                      <jats:italic toggle=\"yes\">N. glabratus<\/jats:italic>\n                      : Wor1 (CAGL0L02453g) and Pth2 (CAGL0C03740g), and found both are upregulated during invasive infection. Genetic deletion experiments revealed that Wor1, but not Pth2, is critical for pathogenicity. A\n                      <jats:italic toggle=\"yes\">wor1<\/jats:italic>\n                      mutant strain showed significantly reduced fungal burden in a murine model of systemic infection and impaired adhesion to human epithelial cells. These virulence defects were not associated with changes in morphology or stress tolerance. RNA-Seq analysis of the\n                      <jats:italic toggle=\"yes\">wor1<\/jats:italic>\n                      mutant during infection identified 400 downregulated and 175 upregulated genes, indicating that Wor1 functions primarily as a transcriptional activator. Among its targets, Wor1 directly bound the promoters of\n                      <jats:italic toggle=\"yes\">PDR1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">UPC2A<\/jats:italic>\n                      . Functional analysis of these downstream targets showed that Upc2A is critical for virulence and adhesion, while Pdr1 expression levels are also critical for these processes. Additionally, Wor1 regulates cell wall proteins involved in host interactions. In conclusion, our study establishes Wor1 as a pivotal regulator of a transcriptional network governing virulence in\n                      <jats:italic toggle=\"yes\">N. glabratus<\/jats:italic>\n                      , controlling host colonization and adhesion by modulating key downstream transcription factors and cell wall components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Fungal infections are a growing threat, especially for patients with weakened immune systems.\n                      <jats:italic toggle=\"yes\">Nakaseomyces glabratus<\/jats:italic>\n                      is particularly dangerous because it resists many common antifungal drugs and is increasingly difficult to treat. Despite this, we know relatively little about how this pathogen causes disease. Here, we identify a critical protein, Wor1, that controls the pathogenicity of\n                      <jats:italic toggle=\"yes\">N. glabratus<\/jats:italic>\n                      . When\n                      <jats:italic toggle=\"yes\">WOR1<\/jats:italic>\n                      is disrupted, the fungus becomes significantly less harmful in animal models and loses much of its ability to adhere to human cells\u2014a crucial first step for infection. Understanding how pathogens activate their disease-causing machinery is essential for finding new drug targets. Because Wor1 and the proteins it controls are specific to fungi and absent in humans, they represent promising candidates for developing therapies that attack the fungus without harming the patient.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01865-26","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:01:13Z","timestamp":1790071273000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A WOPR transcriptional regulatory network controls the virulence of the opportunistic fungal pathogen\n                    <i>Nakaseomyces glabratus<\/i>"],"prefix":"10.1128","author":[{"given":"Jian","family":"Yin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/033vjfk17","id-type":"ROR","asserted-by":"publisher"}],"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan 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