{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:22:33Z","timestamp":1779920553268,"version":"3.53.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100006251","name":"University of Bordeaux","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006251","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Caspofungin is an echinocandin antifungal agent that inhibits synthesis of glucan required for the fungal cell wall. Resistance is mediated by mutation of Fks1 glucan synthase, among which S645P is the most common resistance-associated polymorphism. Rapamycin is a macrolide that inhibits the mechanistic target of rapamycin (mTOR) protein kinase activity. This study investigated the interaction between rapamycin and caspofungin in inhibiting the growth of WT Candida albicans and Fks1 S645P mutant clinical isolate, and WT Candida lusitaniae and genetically engineered isogenic strain with Fks1 S645P mutation at equivalent position.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Interactions between caspofungin and rapamycin were evaluated using the microdilution chequerboard method in liquid medium. The results were analysed using the Loewe additivity model (FIC index, FICI) and the Bliss independence model (response surface, RS, analysis).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Synergy between rapamycin and caspofungin was shown for C. albicans and C. lusitaniae strains by RS analysis of the chequerboard tests. Synergy was observed in strains susceptible and resistant to caspofungin. Weak subinhibitory concentrations of rapamycin were sufficient to restore caspofungin susceptibility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We report here, for the first time, synergy between caspofungin and rapamycin in Candida species. Synergy was shown for strains susceptible and resistant to caspofungin. This study highlights the possible implication of the TOR pathway in sensing antifungal-mediated cell wall stress and in modulating the cellular response to echinocandins in Candida yeasts.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad359","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T17:31:11Z","timestamp":1700674271000},"page":"151-156","source":"Crossref","is-referenced-by-count":7,"title":["Rapamycin and caspofungin show synergistic antifungal effects in caspofungin-susceptible and caspofungin-resistant <i>Candida<\/i> strains <i>in vitro<\/i>"],"prefix":"10.1093","volume":"79","author":[{"given":"Maxime","family":"Lefranc","sequence":"first","affiliation":[{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, 33000 Bordeaux , France"},{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, CHU Bordeaux, 33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Accoceberry","sequence":"additional","affiliation":[{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, 33000 Bordeaux , France"},{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, CHU Bordeaux, 33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Fitton-Ouhabi","sequence":"additional","affiliation":[{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, 33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Biteau","sequence":"additional","affiliation":[{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, 33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-1126","authenticated-orcid":false,"given":"Thierry","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"University Bordeaux, CNRS, Microbiologie Fondamentale et Pathog\u00e9nicit\u00e9 , UMR 5234, 33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"2024010416395768800_dkad359-B1","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci Transl Med"},{"key":"2024010416395768800_dkad359-B2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024010416395768800_dkad359-B3","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/S0140-6736(03)14472-8","article-title":"Echinocandin antifungal drugs","volume":"362","author":"Denning","year":"2003","journal-title":"Lancet"},{"key":"2024010416395768800_dkad359-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12831","article-title":"Mechanisms of echinocandin antifungal drug resistance","volume":"1354","author":"Perlin","year":"2015","journal-title":"Ann N Y Acad Sci"},{"key":"2024010416395768800_dkad359-B5","first-page":"B4698","article-title":"Candida and candidaemia. 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