{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:56:23Z","timestamp":1782276983474,"version":"3.54.5"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      is a major cause of nosocomial fungal infections, often associated with high morbidity and mortality. The rising resistance to antifungal drugs, particularly azoles, underscores the need for new therapeutic strategies. Among resistance mechanisms, alterations in drug targets and overexpression of efflux pump genes play key roles. Efflux inhibitors can enhance the intracellular drug accumulation, thereby restoring antifungal efficacy and preventing resistance development. Drug repurposing offers a cost-effective and time-efficient alternative for identifying new drugs, including efflux inhibitors. In this study, we used an\n                      <jats:italic>in silico<\/jats:italic>\n                      drug repurposing approach to identify approved drugs associated with membrane transport functions and evaluate their efflux-modulating potential\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the DrugBank database, we screened predicted membrane transport proteins in\n                      <jats:italic>C. albicans<\/jats:italic>\n                      and selected those with homology to known drug targets. A subset of drugs, representative of each chemical group, was selected for\n                      <jats:italic>in vitro<\/jats:italic>\n                      screening against the reference strain\n                      <jats:italic>C. albicans<\/jats:italic>\n                      ATCC 90028. We further evaluated the potential adjuvant effect of these drugs on the activity of fluconazole. Finally, the efflux inhibitory effect of the candidate drugs was assessed by real-time fluorometric detection of ethidium bromide accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 245 predicted membrane transport proteins were screened, 51 of which showed homology to known drug targets and were associated with 777 drugs. A subset of 59 drugs was selected for screening. The drug miltefosine showed the lowest minimum inhibitory concentration (MIC; 2 mg\/L), while amlodipine and procainamide demonstrated an adjuvant effect by decreasing the MIC of fluconazole by at least four-fold. Fluorometric assays revealed amlodipine, fluvoxamine and fluoxetine as potential efflux inhibitors in\n                      <jats:italic>C. albicans<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight the potential of these drugs to contribute to the research and development of new therapeutic alternatives aimed at combating antifungal resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1798450","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:40:36Z","timestamp":1779082836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of efflux inhibitors through a drug repurposing strategy in Candida albicans"],"prefix":"10.3389","volume":"16","author":[{"given":"D\u00e9bora","family":"Marques","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisboa, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Santos","family":"Costa","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisboa, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisboa, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jgar.2022.01.030","article-title":"Serotonin reuptake inhibitors effect on fluconazole activity against resistant Candida glabrata strains","volume":"29","author":"Alkhalifa","year":"2022","journal-title":"J. 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