{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:35:36Z","timestamp":1791434136950,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013220","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102454"],"award-info":[{"award-number":["82102454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Antibiotic tolerance, by which susceptible bacteria survive at high bactericide doses, is known to cause treatment failure in clinical practice. However, the impact of antifungal tolerance on clinical outcomes remains poorly understood. Here, we observed that candidemia cases caused by echinocandin-tolerant <jats:italic>Candida tropicalis<\/jats:italic> exhibited higher mortality rates during caspofungin treatment by conducting a comprehensive seven-year retrospective analysis. <jats:italic>C. tropicalis<\/jats:italic> develops tolerance to caspofungin by forming multicellular aggregates, a process linked to defects in cell division, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our omics-based profiling results reveal that <jats:italic>C. tropicalis<\/jats:italic> develops tolerance through the intricate modulation of cell wall integrity and cell division pathways, particularly through the activation of chitin synthesis and the downregulation of cell division-related genes. The overexpression of cell division-related factor Ace2 can suppress the tolerance of <jats:italic>C. tropicalis<\/jats:italic> to caspofungin by delaying the formation of multicellular aggregates. Moreover, calcineurin inhibitors can suppress the tolerance of <jats:italic>C. tropicalis<\/jats:italic> by disrupting these adaptive molecular changes, thereby significantly enhancing the antifungal efficacy of caspofungin in a <jats:italic>Galleria mellonella<\/jats:italic> model. Collectively, our findings provide evidence that <jats:italic>C. tropicalis<\/jats:italic> acquires echinocandin tolerance through morphological alterations, and that inhibiting calcineurin may be a promising method to reduce this tolerance.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013220","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T17:56:37Z","timestamp":1748368597000},"page":"e1013220","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Adaptive morphological changes link to poor clinical outcomes by conferring echinocandin tolerance in Candida tropicalis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-0259","authenticated-orcid":true,"given":"Yongqin","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiwei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengchao","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"issue":"6","key":"ppat.1013220.ref001","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1473-3099(22)00872-6","article-title":"Guideline 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