{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:05:06Z","timestamp":1789621506678,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    The clinical management of\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    (\n                    <jats:italic>C. albicans<\/jats:italic>\n                    ) infections presents considerable problems, intensified by the few therapeutic choices available for this disease. The increasing resistance to fluconazole (FLC) following its widespread clinical use underscores the need for novel therapeutic strategies. Drug repurposing represents a promising approach to expand the antifungal armamentarium, and bortezomib (BTZ), a proteasome inhibitor originally approved for multiple myeloma, has emerged as a candidate for this purpose. This work systematically assessed the synergistic effects of fluconazole (FLC) with bortezomib (BTZ) on the susceptibility of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    , focusing specifically on the planktonic and biofilm development phases. The results exhibited a synergistic antifungal effect of BTZ and FLC against FLC-resistant\n                    <jats:italic>C. albicans<\/jats:italic>\n                    in planktonic cells. The minimal inhibitory concentration (MIC) of BTZ decreased from 64-128 \u00b5g\/ml to 8 \u00b5g\/ml, whereas the MIC of FLC reduced from &amp;gt;128 \u00b5g\/ml to 0.25 \u00b5g\/ml, resulting in a fractional inhibitory concentration index (FICI) of less than 0.5. For FLC-susceptible\n                    <jats:italic>C. albicans<\/jats:italic>\n                    strains, the medication combination exhibited an indifferent interaction, with FICI above 0.5. The combination exhibited synergistic effects against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    during the early stages of biofilm formation (4 and 8\u00a0h). The sessile minimum inhibitory concentration (sMIC) of FLC significantly lowered from \u2265128 \u00b5g\/mL to 0.25 \u00b5g\/mL, whereas the sMIC of BTZ diminished from \u2265128 \u00b5g\/mL to 8-16 \u00b5g\/mL, with a FICI of less than 0.5, signifying significant synergy. Time-kill assays revealed a delayed but sustained inhibitory effect against planktonic cells (24\u201348 h), while CFU enumeration confirmed a concentration-dependent reduction in biofilm viability, with the higher concentration (0.25\u00a0+\u00a016) maintaining efficacy through 24\u00a0h.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , using the\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    (\n                    <jats:italic>G. mellonella<\/jats:italic>\n                    ) infection model, the FLC+BTZ combination significantly improved larval survival, reduced fungal burden, and alleviated tissue damage compared with FLC monotherapy. Mechanistic studies demonstrated that this synergistic effect was mediated by multiple mechanisms, including the suppression of hyphal growth, inhibition of efflux pump activity, and intracellular formation of reactive oxygen species (ROS). These findings highlight the potential of drug repurposing in combating antifungal resistance and provide mechanistic insights into overcoming\n                    <jats:italic>C. albicans<\/jats:italic>\n                    drug resistance.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1856948","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:49:50Z","timestamp":1789620590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antifungal effects and potential mechanism of bortezomib in combination with fluconazole against Candida albicans"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuting","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqing","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijie","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinan","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University","place":["Weihai, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.idc.2010.11.003","article-title":"Nosocomial fungal infections: Epidemiology, infection control, and prevention","volume":"25","author":"Alangaden","year":"2011","journal-title":"Infect. 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