{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:53Z","timestamp":1787022173109,"version":"build-2736575974"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    <jats:italic>Candida auris<\/jats:italic>\n                    is an invasive fungal pathogen, representing a global public health threat. It is characterized by high mortality rates among infected individuals, significant antifungal resistance, and a remarkable ability to persist in healthcare environments. While amphotericin B is one of the most powerful antifungal agents for treating\n                    <jats:italic>Candida<\/jats:italic>\n                    infections, approximately 30% of\n                    <jats:italic>C. auris<\/jats:italic>\n                    isolates demonstrate resistance to it. Thus, the development of novel antifungal therapies is vital for tackling its life-threatening infections. In this study, we identified four HIV protease inhibitors (atazanavir, saquinavir, lopinavir and ritonavir) as strong potentiators of amphotericin B against\n                    <jats:italic>C. auris<\/jats:italic>\n                    . A synergistic effect between HIV protease inhibitors and amphotericin B was observed against 15\n                    <jats:italic>C. auris<\/jats:italic>\n                    isolates with fractional inhibitory concentration index (FICI) ranging from 0.09 to 0.50. Additionally, the combinations between HIV protease inhibitors and amphotericin B showed fungicidal effect, significantly reducing the viable cell count in the time-kill assay within 6 hours. Furthermore, the combinations inhibited biofilm formation of\n                    <jats:italic>C. auris<\/jats:italic>\n                    by 60\u201375% and exhibited a remarkable suppression of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    hyphae. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    treatment with HIV protease inhibitors combined with amphotericin B resulted in a significant reduction of\n                    <jats:italic>C. auris<\/jats:italic>\n                    colony-forming units (CFU) by 1.7\u20132.6 Log\n                    <jats:sub>10<\/jats:sub>\n                    in the\n                    <jats:italic>C. elegans<\/jats:italic>\n                    model. These findings suggest that HIV protease inhibitors, in combination with amphotericin B, are promising candidates for the development of novel antifungal drugs to treat\n                    <jats:italic>Candida<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0324080","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T13:28:14Z","timestamp":1748525294000},"page":"e0324080","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["HIV protease inhibitors restore amphotericin B activity against Candida"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5735-9223","authenticated-orcid":true,"given":"Yehia","family":"Elgammal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab A.","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"1","key":"pone.0324080.ref001","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab593","article-title":"Prevalence and healthcare burden of fungal infections in the United States, 2018","volume":"9","author":"E Rayens","year":"2022","journal-title":"Open Forum Infect Dis"},{"issue":"9","key":"pone.0324080.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/jof9090913","article-title":"An overview on Candida auris in healthcare settings","volume":"9","author":"ML Cristina","year":"2023","journal-title":"J Fungi"},{"issue":"1","key":"pone.0324080.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/mmy\/myy054","article-title":"Candida 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