{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:42:12Z","timestamp":1790505732487,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Postgraduate Research and Innovation Plan Project of Jiangsu Province","award":["KYLX16_1283"],"award-info":[{"award-number":["KYLX16_1283"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81330035"],"award-info":[{"award-number":["81330035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2017,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            remains limited. In this study, we found that two endoplasmic reticulum-localized sterol C-24 reductases encoded by both\n            <jats:italic>erg4A<\/jats:italic>\n            and\n            <jats:italic>erg4B<\/jats:italic>\n            homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. Loss of one homolog of Erg4 induces the overexpression of the other one, accompanied by almost normal ergosterol synthesis and wild-type colony growth. However, double deletions of\n            <jats:italic>erg4A<\/jats:italic>\n            and\n            <jats:italic>erg4B<\/jats:italic>\n            completely block the last step of ergosterol synthesis, resulting in the accumulation of ergosta-5,7,22,24(28)-tetraenol, a precursor compound of ergosterol. Further studies indicate that\n            <jats:italic>erg4A<\/jats:italic>\n            and\n            <jats:italic>erg4B<\/jats:italic>\n            are required for conidiation but not for hyphal growth. Importantly, the \u0394\n            <jats:italic>erg4A<\/jats:italic>\n            \u0394\n            <jats:italic>erg4B<\/jats:italic>\n            mutant still demonstrates wild-type virulence in a compromised mouse model but displays remarkable increased susceptibility to antifungal azoles. Our data suggest that inhibitors of Erg4A and Erg4B may serve as effective candidates for adjunct antifungal agents with azoles.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Knowledge of the ergosterol biosynthesis pathway in the human opportunistic pathogen\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            is useful for designing and finding new antifungal drugs. In this study, we demonstrated that the endoplasmic reticulum-localized sterol C-24 reductases Erg4A and Erg4B are required for conidiation via regulation of ergosterol biosynthesis. Moreover, inactivation of both Erg4A and Erg4B results in hypersensitivity to the clinical guideline-recommended antifungal drugs itraconazole and voriconazole. Therefore, our finding indicates that inhibition of Erg4A and Erg4B might be an effective approach for alleviating\n            <jats:named-content content-type=\"genus-species\">A. fumigatus<\/jats:named-content>\n            infection.\n          <\/jats:p>","DOI":"10.1128\/aem.02924-16","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T17:51:06Z","timestamp":1482515466000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus"],"prefix":"10.1128","volume":"83","author":[{"given":"Nanbiao","family":"Long","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuqiong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.2.310"},{"key":"e_1_3_3_3_2","first-page":"986","article-title":"Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003)","volume":"91","author":"Chamilos G","year":"2006","unstructured":"Chamilos G LunaM LewisRE BodeyGP ChemalyR TarrandJJ SafdarA RaadII KontoyiannisDP. 2006. 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