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This study evaluated REV combined with triazoles (itraconazole, ITR; voriconazole, VOR; posaconazole, POS) against 30 clinical\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    isolates (14\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    , 12\n                    <jats:italic>A. flavus<\/jats:italic>\n                    , 4\n                    <jats:italic>A. terreus<\/jats:italic>\n                    ) using MIC and FICI assays. REV demonstrated dose-dependent synergy (FICI\u2009\u2264\u20090.5) with POS in 90% of isolates (27\/30), reducing MIC values by 4\u20138fold, while synergy with ITR occurred in 20% (6\/30). Species-specific analysis revealed highest efficacy against\n                    <jats:italic>A. flavus<\/jats:italic>\n                    (91.7%, 11\/12) and\n                    <jats:italic>A. terreus<\/jats:italic>\n                    (100%, 4\/4). No synergy was observed with VOR. Furthermore, the mechanisms underlying the synergistic effects of REV with triazoles were investigated using an\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    major facilitator superfamily (MFS) transporter gene-deficient strains. Knockout strains\n                    <jats:italic>\u0394AF-MFS32<\/jats:italic>\n                    and\n                    <jats:italic>\u0394AF-MFS35<\/jats:italic>\n                    , selected from our MFS transporter gene-deficient strains, showed a abolishment of synergistic interaction when combined with REV and the triazoles ITR and POS. Suggesting a functional link between these transporters and the drug interaction. Disk diffusion and efflux pump assays corroborated these findings (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). These in vitro results identify REV\u2009+\u2009POS as a promising combination against\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    , though in vivo studies and mechanistic validation of transporter inhibition are warranted.\n                  <\/jats:p>\n                  <jats:p>\n                    Overall, this study shows that the potassium-competitive acid pump antagonist REV exhibits synergistic antifungal activity with triazoles in treating\n                    <jats:italic>Aspergillus<\/jats:italic>\n                    infections. The MFS transporter\n                    <jats:italic>AF-MFS32<\/jats:italic>\n                    and\n                    <jats:italic>AF-MFS35<\/jats:italic>\n                    are implicated as possible targets mediating the synergistic interaction between REV and these antifungal drugs.\n                  <\/jats:p>","DOI":"10.1186\/s12866-025-04471-w","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:11:59Z","timestamp":1762341119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro combination effects and mechanisms of Revaprazan with Triazole antifungal drugs on Aspergillus"],"prefix":"10.1186","volume":"25","author":[{"given":"Wenxu","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijia","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"issue":"9","key":"4471_CR1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","volume":"20","author":"MC Fisher","year":"2022","unstructured":"Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. 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Approval was granted by the Ethics Committee of Jingzhou Hospital Afliated to Yangtze University.And obtain informed consent from all participants in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"715"}}