{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:16Z","timestamp":1792788976964,"version":"4.5.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2303004"],"award-info":[{"award-number":["2022YFC2303004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["202101070007-E00094"],"award-info":[{"award-number":["202101070007-E00094"]}],"id":[{"id":"https:\/\/ror.org\/05tewj457","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82020108032"],"award-info":[{"award-number":["82020108032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["23ZR1449500"],"award-info":[{"award-number":["23ZR1449500"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Exposure to endoplasmic reticulum (ER) stress can drive the emergence of antifungal resistance in pathogenic fungi, but the underlying mechanisms remain poorly understood. Here, we show that treatment of\n                    <jats:italic>Candida auris<\/jats:italic>\n                    B12037 (clade 3) with the ER stressor tunicamycin selects for survivors with acquired resistance to fluconazole and, in a subset, tolerance to caspofungin. Pharmacological inhibition revealed that caspofungin tolerance, but not fluconazole resistance, requires the Hsp90-calcineurin axis. RNA-seq analysis of the parental strain exposed to tunicamycin uncovered a coordinated stress response characterized by up-regulation of cell wall biosynthesis, transmembrane transport, and autophagy, alongside global repression of translation and energy metabolism. In the resistant survivors, fluconazole resistance correlated with up-regulation of the efflux pump\n                    <jats:italic>MDR1<\/jats:italic>\n                    , with isolate #10 additionally exhibiting\n                    <jats:italic>ERG11<\/jats:italic>\n                    overexpression. Caspofungin tolerance in isolate #10 was associated with up-regulation of multiple chitin synthase genes (\n                    <jats:italic>CHS1<\/jats:italic>\n                    ,\n                    <jats:italic>CHS3<\/jats:italic>\n                    ,\n                    <jats:italic>CHS5<\/jats:italic>\n                    ), suggesting chitin-mediated cell wall remodeling. Isolate #19 displayed a distinct pattern, indicating alternative mechanisms of caspofungin tolerance. These findings reveal that ER stress selects for\n                    <jats:italic>C. auris<\/jats:italic>\n                    survivors with divergent antifungal resistance profiles through distinct molecular pathways, highlighting the potential for stress-induced evolution of multidrug resistance in this critical pathogen.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1845986","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:33:39Z","timestamp":1790314419000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ER stress selects for Candida auris survivors with acquired fluconazole resistance and caspofungin tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Feng","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuliu","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinli","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathogen-Host Interaction (MOE), Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13073-014-0100-8","article-title":"YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens","volume":"6","author":"Abbey","year":"2014","journal-title":"Genome Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11046-025-00974-2","article-title":"Comparative clinical characteristics and outcomes of Candida (Candidozyma) auris vs. non-C. auris candidemia in non-neutropenic patients in South India","volume":"190","author":"Athavale-Wad","year":"2025","journal-title":"Mycopathologia"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e0030025","DOI":"10.1128\/aac.00300-25","article-title":"Mutations in TAC1B drive increased CDR1 and MDR1 expression and azole resistance in Candida auris","volume":"69","author":"Barker","year":"2025","journal-title":"Antimicrob. 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