{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:17:18Z","timestamp":1788369438245,"version":"build-2803163510"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"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":["82404705"],"award-info":[{"award-number":["82404705"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Invasive fungal infections (IFIs) remain a major global health threat due to limited therapeutic options and rising azole resistance. NT-a9 is a novel triazole antifungal with potent activity against\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      species via strong inhibition of ergosterol biosynthesis.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , NT-a9 exhibited potent and sustained antifungal activity against clinical isolates, with superior potency compared to fluconazole (FLC). It also displayed a prolonged post-antifungal effect (PAFE) against most\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      species, a property rarely seen in conventional azoles. Resistance profiling demonstrated that NT-a9 possesses a high genetic barrier, fully suppressing resistant mutant emergence in\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      species and maintaining stable susceptibility in\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      during 28 days of continuous exposure. NT-a9 retained potent activity against FLC-resistant\n                      <jats:italic toggle=\"yes\">Cryptococcus neoformans<\/jats:italic>\n                      and multidrug-resistant\n                      <jats:italic toggle=\"yes\">Candida auris<\/jats:italic>\n                      , with minimal influence from drug efflux mechanisms. In murine invasive candidiasis, a single low dose of NT-a9 achieved 100% survival and markedly reduced renal fungal burden, significantly outperforming FLC. NT-a9 also substantially improved survival in mice infected with FLC-resistant\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      . Mechanistically, NT-a9 binds Erg11 with much higher affinity than FLC by forming key hydrogen bonds with Gly307 and His377, leading to irreversible ergosterol depletion, toxic sterol accumulation, and severe fungal membrane damage. Transcriptomic analysis further confirmed that NT-a9 extensively disrupts sterol biosynthesis and triggers compensatory gene expression that reinforces its antifungal action. As a novel triazole integrating long-lasting efficacy, a high resistance barrier, and potent activity against pan-azole-resistant pathogens, NT-a9 represents a promising clinical candidate for treating IFIs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00768-26","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:46:35Z","timestamp":1785937595000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["NT-A9, a new triazole, exhibits potent antifungal activity against\n                    <i>Candida<\/i>\n                    and\n                    <i>Cryptococcus<\/i>\n                    species through potent ergosterol biosynthesis 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