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Invasive infections caused by\n              <jats:italic>C. auris<\/jats:italic>\n              are usually associated with remarkable morbidity and mortality. For many years, amphotericin B (AmB) remained the most efficient and the last line of treatment against most hard-to-treat fungal infections. However, strains of\n              <jats:italic>C. auris<\/jats:italic>\n              possess extraordinary resistance to most antifungal agents, including AmB. In this study, we screened ~2,600 FDA-approved drugs and clinical compounds to identify the antiemetic drug rolapitant as a promising enhancer to AmB against\n              <jats:italic>C. auris<\/jats:italic>\n              . Rolapitant exhibited potent synergistic interactions with AmB against all tested (29\/29)\n              <jats:italic>C. auris<\/jats:italic>\n              isolates. In a time-kill assay, rolapitant restored the fungicidal activity of AmB within 4 h. Additionally, the synergistic relationship between rolapitant and AmB was observed against other medically crucial\n              <jats:italic>Candida<\/jats:italic>\n              ,\n              <jats:italic>Cryptococcus,<\/jats:italic>\n              and\n              <jats:italic>Aspergillus<\/jats:italic>\n              species. A transcriptomic study revealed that exposure to rolapitant affects oxidation reduction processes, ion transporters, and ATP production. Rolapitant triggers an elevation in cytosolic and mitochondrial calcium levels and induces oxidative stress within fungal cells. An ATP luminescence assay confirmed that rolapitant, at sub-inhibitory concentrations, significantly interfered with ATP production in\n              <jats:italic>C. auris<\/jats:italic>\n              . Moreover, rolapitant enhanced the\n              <jats:italic>in vivo<\/jats:italic>\n              activity of AmB in a mouse model of disseminated\n              <jats:italic>C. auris<\/jats:italic>\n              infection, as the combination reduced the fungal burden in murine kidneys by ~1 log (~90%) colony forming units. Our findings warrant further investigation of using rolapitant to overcome AmB resistance in\n              <jats:italic>C. auris<\/jats:italic>\n              and other fungal species.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00556-24","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T13:03:44Z","timestamp":1728565424000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Overcoming amphotericin B resistance in\n            <i>Candida auris<\/i>\n            using the antiemetic drug rolapitant"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-5935","authenticated-orcid":true,"given":"Ehab A.","family":"Salama","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"},{"name":"Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehia","family":"Elgammal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"},{"name":"Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar M.","family":"Utturkar","sequence":"additional","affiliation":[{"name":"Purdue Institute for Cancer Research, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia A.","family":"Lanman","sequence":"additional","affiliation":[{"name":"Purdue Institute for Cancer Research, Purdue University, West Lafayette, Indiana, USA"},{"name":"Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony R.","family":"Hazbun","sequence":"additional","affiliation":[{"name":"Purdue Institute for Cancer Research, Purdue University, West Lafayette, Indiana, USA"},{"name":"Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0458","authenticated-orcid":true,"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"},{"name":"Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011136"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55379-1"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00826-w"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof5030067"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01397-19"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019711"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00294-8"},{"key":"e_1_3_5_9_2","unstructured":"World Health Organization. 2022. 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