{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:24:19Z","timestamp":1791422659200,"version":"4.3.3"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Azoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. This study identified a bZIP transcription factor, ADS-4 (\n            <jats:italic>a<\/jats:italic>\n            ntifungal\n            <jats:italic>d<\/jats:italic>\n            rug\n            <jats:italic>s<\/jats:italic>\n            ensitive-4), as a new regulator of adaptive responses and resistance to antifungal azoles. Transcription of\n            <jats:italic>ads-4<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neurospora crassa<\/jats:named-content>\n            cells increased when they were subjected to ketoconazole treatment, whereas the deletion of\n            <jats:italic>ads-4<\/jats:italic>\n            resulted in hypersensitivity to ketoconazole and fluconazole. In contrast, the overexpression of\n            <jats:italic>ads-4<\/jats:italic>\n            increased resistance to fluconazole and ketoconazole in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. crassa<\/jats:named-content>\n            . Transcriptome sequencing (RNA-seq) analysis, followed by quantitative reverse transcription (qRT)-PCR confirmation, showed that ADS-4 positively regulated the transcriptional responses of at least six genes to ketoconazole stress in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. crassa<\/jats:named-content>\n            . The gene products of four ADS-4-regulated genes are known contributors to azole resistance, including the major efflux pump CDR4 (Pdr5p ortholog), an ABC multidrug transporter (NcAbcB), sterol C-22 desaturase (ERG5), and a lipid transporter (NcRTA2) that is involved in calcineurin-mediated azole resistance. Deletion of the\n            <jats:italic>ads-4<\/jats:italic>\n            -homologous gene Af\n            <jats:italic>ads-4<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            caused hypersensitivity to itraconazole and ketoconazole, which suggested that ADS-4 is a functionally conserved regulator of adaptive responses to azoles. This study provides important information on a new azole resistance factor that could be targeted by a new range of antifungal pesticides and drugs.\n          <\/jats:p>","DOI":"10.1128\/aac.00542-15","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T01:45:36Z","timestamp":1435023936000},"page":"5396-5404","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Transcription Factor ADS-4 Regulates Adaptive Responses and Resistance to Antifungal Azole Stress"],"prefix":"10.1128","volume":"59","author":[{"given":"Kangji","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"},{"name":"University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenying","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"},{"name":"University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyun","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1514-6374","authenticated-orcid":false,"given":"Cheng","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/bs.aambs.2014.09.001","article-title":"The evolution of fungicide resistance","volume":"90","author":"Lucas JA","year":"2015","unstructured":"Lucas JA, Hawkins NJ, Fraaije BA. 2015. 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