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Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 \u03bcg\/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 \u03bcg\/ml, with a fractional inhibitory concentration index of &lt;0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of\n            <jats:italic>ERG11<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>\n            but not in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            , despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast.\n          <\/jats:p>","DOI":"10.1128\/aac.06017-11","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T06:55:27Z","timestamp":1336460127000},"page":"3785-3796","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis"],"prefix":"10.1128","volume":"56","author":[{"given":"Alessandro","family":"Fiori","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Flanders Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, Leuven, Belgium"},{"name":"Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Van Dijck","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Flanders Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, Leuven, Belgium"},{"name":"Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780500138971"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000217"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/1097-0061(20000915)16:12<1121::AID-YEA614>3.0.CO;2-U","article-title":"Evaluation of the CaMAL2 promoter for regulated expression of genes in Candida albicans","volume":"16","author":"Backen AC","year":"2000","unstructured":"BackenAC . 2000. 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