{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:40:39Z","timestamp":1777030839901,"version":"3.51.4"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI73896, AI93257"],"award-info":[{"award-number":["AI73896, AI93257"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UC6-AI058607"],"award-info":[{"award-number":["UC6-AI058607"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Duke University Precision Genomics Collaboratory"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of\n              <jats:italic>Cryptococcus neoformans<\/jats:italic>\n              and\n              <jats:italic>Candida albicans<\/jats:italic>\n              infection in combination with fluconazole\u2014a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with\n              <jats:italic>C. neoformans<\/jats:italic>\n              and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 \u00b1 0.289 log\n              <jats:sub>10<\/jats:sub>\n              reduction) and lung (mean 1.72 \u00b1 0.399 log\n              <jats:sub>10<\/jats:sub>\n              reduction) compared to fluconazole treatment on a conventional diet. During\n              <jats:italic>C. albicans<\/jats:italic>\n              infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 \u00b1 0.770 log\n              <jats:sub>10<\/jats:sub>\n              -reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both\n              <jats:italic>C. neoformans<\/jats:italic>\n              and\n              <jats:italic>C. albicans<\/jats:italic>\n              infection and could have practical and promising treatment implications.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Invasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both\n                <jats:italic>C. neoformans<\/jats:italic>\n                and\n                <jats:italic>C. albicans<\/jats:italic>\n                in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00649-24","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T13:00:33Z","timestamp":1713186033000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-8278","authenticated-orcid":false,"given":"Julia R.","family":"Palmucci","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blake E.","family":"Sells","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7813-5616","authenticated-orcid":false,"given":"Charles D.","family":"Giamberardino","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dena L.","family":"Toffaletti","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baodi","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohannes G.","family":"Asfaw","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura G.","family":"Dubois","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Duke University, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Duke University, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Theriot","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiley A.","family":"Schell","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool Health Partners, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Tenor","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-3676","authenticated-orcid":false,"given":"John R.","family":"Perfect","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00692-8"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00499-6"},{"key":"e_1_3_5_5_2","first-page":"57","volume-title":"Microbial siderophores: markers of infectious diseases","author":"Dobi\u00e1\u0161 R","year":"2020","unstructured":"Dobi\u00e1\u0161 R, Havl\u00ed\u010dek V. 2020. 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