{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:37:03Z","timestamp":1792132623524,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013363","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2021-NR058017"],"award-info":[{"award-number":["RS-2021-NR058017"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2021-NR056582"],"award-info":[{"award-number":["RS-2021-NR056582"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-00555365"],"award-info":[{"award-number":["RS-2025-00555365"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-02215093"],"award-info":[{"award-number":["RS-2025-02215093"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2022-NR072215"],"award-info":[{"award-number":["RS-2022-NR072215"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2021-NF000550"],"award-info":[{"award-number":["RS-2021-NF000550"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2024-00345184"],"award-info":[{"award-number":["RS-2024-00345184"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yonsei Signature Research Cluster Program","award":["2025-22-0015"],"award-info":[{"award-number":["2025-22-0015"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>\n                      <jats:italic>Candida auris<\/jats:italic>\n                    <\/jats:italic>\n                    , an emerging fungal pathogen characterized by its multidrug resistance and high mortality rates, poses a significant public health challenge. Despite its importance, the signaling pathways governing virulence and antifungal resistance in\n                    <jats:italic>\n                      <jats:italic>C. auris<\/jats:italic>\n                    <\/jats:italic>\n                    remain poorly understood. This study investigates the calcineurin pathway in\n                    <jats:italic>\n                      <jats:italic>C. auris<\/jats:italic>\n                    <\/jats:italic>\n                    , critical for virulence and antifungal resistance in other fungal pathogens. Calcineurin, a calcium\/calmodulin-dependent protein phosphatase, comprises a catalytic subunit (Cna1) and a regulatory subunit (Cnb1) in\n                    <jats:italic>\n                      <jats:italic>C. auris<\/jats:italic>\n                    <\/jats:italic>\n                    . Our findings reveal that deletion of\n                    <jats:italic>CNA1<\/jats:italic>\n                    or\n                    <jats:italic>CNB1<\/jats:italic>\n                    disrupts extreme thermotolerance and cell membrane and wall integrity, leading to increased susceptibility to azoles and echinocandins. Moreover, we identified a downstream transcription factor, Crz1, which plays a central role in this pathway in other fungal species. Deletion of\n                    <jats:italic>CRZ1<\/jats:italic>\n                    resulted in thermotolerance and membrane integrity defects comparable to those of\n                    <jats:italic>\n                      <jats:italic>cna1<\/jats:italic>\n                    <\/jats:italic>\n                    \u0394 and\n                    <jats:italic>\n                      <jats:italic>cnb1<\/jats:italic>\n                    <\/jats:italic>\n                    \u0394 mutants, along with increased azole susceptibility. Supporting it, fluconazole treatment induced Crz1 nuclear translocation in a Cna1-dependent manner. However, unlike\n                    <jats:italic>\n                      <jats:italic>cna1<\/jats:italic>\n                    <\/jats:italic>\n                    \u0394 and\n                    <jats:italic>\n                      <jats:italic>cnb1<\/jats:italic>\n                    <\/jats:italic>\n                    \u0394 mutants, the\n                    <jats:italic>\n                      <jats:italic>crz1<\/jats:italic>\n                    <\/jats:italic>\n                    \u0394 mutant displayed increased resistance to echinocandins, suggesting the opposing roles for Crz1 in regulating cell wall integrity. Nevertheless, echinocandins also promoted Crz1 nuclear translocation via Cna1, underscoring the complex regulatory mechanisms at play. Cna1 was found to be required for virulence in both the\n                    <jats:italic>\n                      <jats:italic>Drosophila<\/jats:italic>\n                    <\/jats:italic>\n                    systemic infection model and the murine skin infection model. However, in a systemic murine infection model, both calcineurin and Crz1 appeared dispensable for\n                    <jats:italic>\n                      <jats:italic>C. auris<\/jats:italic>\n                    <\/jats:italic>\n                    virulence. Our findings highlight that the evolutionarily conserved calcineurin pathway employs distinct regulatory mechanisms to perform divergent roles in regulating extreme thermotolerance, cell wall and membrane integrity, antifungal drug resistance, and virulence in\n                    <jats:italic>\n                      <jats:italic>C. auris<\/jats:italic>\n                    <\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013363","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T17:54:23Z","timestamp":1753725263000},"page":"e1013363","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["The calcineurin pathway regulates extreme thermotolerance, cell membrane and wall integrity, antifungal resistance, and virulence in Candida auris"],"prefix":"10.1371","volume":"21","author":[{"given":"Hyunjin","family":"Cha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doyeon","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Seong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ah","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Tae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-5752","authenticated-orcid":true,"given":"Yong-Sun","family":"Bahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"issue":"7","key":"ppat.1013363.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global 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