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Even dihydrofolate reductase (DHFR), a well-characterized and historically important drug target, has not been conclusively validated as an antifungal target. Here, we demonstrate that repression of DHFR inhibits growth of\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            , a major human fungal pathogen. Methotrexate, an antifolate, also inhibits growth but through pH-dependent activity. In addition, we show that\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            has a limited ability to take up or utilize exogenous folates as only the addition of high concentrations of folinic acid restored growth in the presence of methotrexate. Finally, we show that repression of DHFR in a mouse model of infection was sufficient to eliminate host mortality. Our work conclusively establishes DHFR as a valid antifungal target in\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/msphere.00374-20","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T13:42:13Z","timestamp":1593006133000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Dihydrofolate Reductase Is a Valid Target for Antifungal Development in the Human Pathogen\n            <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"5","author":[{"given":"Christian","family":"DeJarnette","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology and Biochemistry, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Luna-Tapia","sequence":"additional","affiliation":[{"name":"National Program in Biotechnology, Ministry of Science, Technology and Innovation, Bogota, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanna R.","family":"Estredge","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-3130","authenticated-orcid":false,"given":"Glen E.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy776"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S118892"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3062.1999.010406.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/11585270-000000000-00000"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/24.2.235"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066906"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411173312001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc10514"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-11-261"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67490-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy827"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/598933"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021585"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/520980"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040446"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01588-17"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00298-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800223-0.00004-9"},{"key":"e_1_3_2_21_2","first-page":"2S87","article-title":"New mechanisms for an old drug; DHFR- and non-DHFR-mediated effects of methotrexate in cancer cells","volume":"25","author":"Neradil J","year":"2012","unstructured":"Neradil J, Pavlasova G, Veselska R. 2012. 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