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The mortality rate of aspergillosis remains high despite antifungal treatments, with azole antifungals, such as voriconazole, being the primary treatment. However, resistance to azoles is increasing, partly because of environmental exposure to agricultural fungicides. In a previous study, we identified the protein RttA to be involved in azole susceptibility. To further understand the role of RttA in azole resistance, we conducted RNA-Seq analysis and functional analyses by constructing RttA deletion and overexpression strains. The transcriptome data revealed that RttA contains a Zn\n                      <jats:sub>2<\/jats:sub>\n                      -Cys\n                      <jats:sub>6<\/jats:sub>\n                      domain and may function as a transcription factor. Furthermore, six genes, including a \u03b3-glutamyl transpeptidase gene (\n                      <jats:italic toggle=\"yes\">ggtA<\/jats:italic>\n                      ) and a homolog of factor C (\n                      <jats:italic toggle=\"yes\">facC<\/jats:italic>\n                      ), were shown to be putatively regulated by RttA. These findings suggest that RttA is involved in azole resistance by regulating several genes, highlighting its potential as a target for developing antifungal strategies against\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study identified RttA as a Zn\n                        <jats:sub>2<\/jats:sub>\n                        -Cys\n                        <jats:sub>6<\/jats:sub>\n                        transcription factor in\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        , a critical pathogen that causes aspergillosis. RttA influences azole susceptibility. Our results demonstrated that the deletion of RttA increases susceptibility to azoles, whereas its overexpression enhances resistance. This discovery is crucial because the mechanism underlying azole resistance has not yet been fully elucidated. Hence, understanding the role of RttA provides insights into resistance mechanisms and potential targets for new therapeutic strategies, thereby addressing the urgent need for effective treatments against azole-resistant\n                        <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                        strains.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01810-25","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:46:06Z","timestamp":1755801966000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["RttA, a Zn\n                    <sub>2<\/sub>\n                    -Cys\n                    <sub>6<\/sub>\n                    transcription factor in\n                    <i>Aspergillus fumigatus<\/i>\n                    , contributes to azole resistance"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2822-2767","authenticated-orcid":true,"given":"Takahito","family":"Toyotome","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/053d3tv41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmaceutical Sciences, School of Pharmacy at Narita, International University of Health and Welfare","place":["Narita, Japan"]},{"id":[{"id":"https:\/\/ror.org\/02t9fsj94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine","place":["Obihiro, Japan"]},{"id":[{"id":"https:\/\/ror.org\/02t9fsj94","id-type":"ROR","asserted-by":"publisher"}],"name":"Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine","place":["Obihiro, Japan"]},{"name":"Medical Mycology Research Center, Chiba University","place":["Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-1035","authenticated-orcid":true,"given":"Hiroki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center, Chiba University","place":["Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-2937","authenticated-orcid":true,"given":"Akira","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center, Chiba University","place":["Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-3914","authenticated-orcid":true,"given":"Daisuke","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Medical Mycology Research Center, Chiba University","place":["Chiba, Japan"]},{"id":[{"id":"https:\/\/ror.org\/02956yf07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life and Environmental Sciences, University of Tsukuba","place":["Tsukuba, Japan"]},{"name":"Microbiology Research Center for Sustainability (MiCS), University of Tsukuba","place":["Tsukuba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"How common are fungal diseases? \u2013 Fungal Infection Trust. 2021. 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