{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:06:26Z","timestamp":1790712386217,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"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":"crossref","award":["82270015 82302577 82304209 81973983"],"award-info":[{"award-number":["82270015 82302577 82304209 81973983"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Invasive candidiasis has emerged as a significant healthcare challenge, with a rising incidence rate attributed to the widespread use of organ transplantation, chemotherapy, immunosuppressants, and broad-spectrum antibiotics. The increasing prevalence of drug-resistant strains, particularly among\n              <jats:italic>Candida tropicalis<\/jats:italic>\n              , has necessitated the exploration of novel therapeutic strategies. Our study investigated the synergistic effects of minocycline (MIN) combined with fluconazole (FLC) against FLC-resistant\n              <jats:italic>C. tropicalis<\/jats:italic>\n              , both\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              . The\n              <jats:italic>in vitro<\/jats:italic>\n              synergistic activity of MIN and FLC was evaluated using checkerboard titration and time-kill assays. The\n              <jats:italic>Galleria mellonella<\/jats:italic>\n              larvae and mouse model were employed to assess\n              <jats:italic>in vivo<\/jats:italic>\n              efficacy, with histopathological examination and fungal burden quantification. Whole-genome and RNA sequencing elucidated the synergistic mechanisms observed. The FLC\/MIN combination significantly lowered the minimum inhibitory concentration (MIC) and improved fungicidal activity, as evidenced by enhanced survival rates and reduced fungal burden in\n              <jats:italic>G. mellonella<\/jats:italic>\n              larvae and mouse models. Histopathological analysis confirmed less tissue damage and fungal load with combination therapy. RNA sequencing analysis suggested that the impact of MIN on amino acid metabolism contributes to the synergistic effects. This approach holds promise for treating FLC-resistant\n              <jats:italic>C. tropicalis<\/jats:italic>\n              by increasing antifungal efficacy and reducing drug resistance risks, warranting further clinical exploration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              This study highlights the potential of minocycline and fluconazole combination therapy in combating drug-resistant\n              <jats:italic>Candida tropicalis<\/jats:italic>\n              . It shows promising\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              synergistic effects, reducing MIC and enhancing fungicidal activity. Further clinical trials are needed to validate its efficacy in treating FLC-resistant\n              <jats:italic>C. tropicalis<\/jats:italic>\n              infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03185-24","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T16:19:51Z","timestamp":1744647591000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic antifungal activity of minocycline as an effective augmenting agent of fluconazole against drug-resistant\n            <i>Candida tropicalis<\/i>"],"prefix":"10.1128","volume":"13","author":[{"given":"Yun-Zhu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases & Anhui Province Key Laboratory of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]},{"name":"Anhui Center for 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