{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:44:48Z","timestamp":1790063088529,"version":"4.0.1"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The National Natural Science Founadation of China","award":["82073899"],"award-info":[{"award-number":["82073899"]}]},{"name":"The National Key Research and Research Development Programs of China","award":["2018YFC0311003"],"award-info":[{"award-number":["2018YFC0311003"]}]},{"name":"The Hospital-level Foundation of the Affiliated Taizhou People's Hospital of Nanjing Medical University","award":["ZL202206"],"award-info":[{"award-number":["ZL202206"]}]},{"name":"The Changzhou Science and Technology Project Fund","award":["CJ20210012"],"award-info":[{"award-number":["CJ20210012"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,1,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Opportunistic fungal infections, particularly caused by\n            <jats:italic>Candida albicans<\/jats:italic>\n            , remain a common cause of high morbidity and mortality in immunocompromised patients. The escalating prevalence of antifungal drug resistance necessitates the immediate exploration of alternative treatment strategies to combat these life-threatening fungal diseases. In this study, we investigated the antifungal efficacy of firsocostat, a human acetyl-CoA carboxylase (ACC) inhibitor, against\n            <jats:italic>C. albicans<\/jats:italic>\n            . Firsocostat alone displayed moderate antifungal activity, while combining it with voriconazole, itraconazole, or amphotericin B exhibited synergistic effects across almost all drug-sensitive and drug-resistant\n            <jats:italic>C. albicans<\/jats:italic>\n            strains tested. These observed synergies were further validated in two mouse models of oropharyngeal and systemic candidiasis, where the combination therapies demonstrated superior fungicidal effects compared to monotherapy. Moreover, firsocostat was shown to directly bind to\n            <jats:italic>C. albicans<\/jats:italic>\n            ACC and inhibit its enzymatic activity. Sequencing spontaneous firsocostat-resistant mutants revealed mutations mapping to\n            <jats:italic>C. albicans<\/jats:italic>\n            ACC, confirming that firsocostat has retained its target in\n            <jats:italic>C. albicans<\/jats:italic>\n            . Overall, our findings suggest that repurposing firsocostat, either alone or in combination with other antifungal agents, holds promising potential in the development of antifungal drugs and the treatment of candidiasis.\n          <\/jats:p>","DOI":"10.1128\/aac.01131-23","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T14:00:16Z","timestamp":1701266416000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination"],"prefix":"10.1128","volume":"68","author":[{"given":"Tianyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University , Nanjing, Jiangsu, China"},{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu, China"},{"name":"Department of Respiratory and Critical Care Medicine, Taizhou People\u2019s Hospital Affiliated to Nanjing Medical University , Taizhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University , Nanjing, Jiangsu, China"},{"name":"Department of Respiratory Medicine, The Second Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keao","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University , Nanjing, Jiangsu, 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