{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:50:03Z","timestamp":1791355803869,"version":"4.3.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Candidozyma auris<\/jats:italic>\n is an emerging multidrug-resistant fungal pathogen, and widespread fluconazole (FLC) resistance severely limits clinical treatment options. Overexpression of the efflux transporter\n CDR1<\/jats:italic>\n represents a major driver of azole resistance; however, how oxidative stress modulates this process remains poorly understood. This study aimed to identify novel regulators that connect oxidative stress adaptation with azole resistance in\n C. auris<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We constructed\n SLA1<\/jats:italic>\n deletion mutants of\n C. auris<\/jats:italic>\n .\n SLA1<\/jats:italic>\n encodes a conserved regulator of cytoskeletal organization and membrane trafficking. We evaluated mitochondrial homeostasis, mtROS accumulation, and\n CDR1<\/jats:italic>\n expression. Pharmacological mitochondrial perturbation was used to disentangle the individual effects of ROS accumulation and mitochondrial dysfunction on FLC resistance. We further assessed cell envelope integrity,\n in vivo<\/jats:italic>\n virulence, and the transcriptional correlation between\n SLA1<\/jats:italic>\n and\n CDR1<\/jats:italic>\n using clinical isolates.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n SLA1<\/jats:italic>\n deletion triggered mitochondrial dysfunction, increased mtROS accumulation, upregulated\n CDR1<\/jats:italic>\n , and enhanced azole resistance. Pharmacological disruption of mitochondria further raised ROS levels yet suppressed\n CDR1<\/jats:italic>\n , depleted ATP, accumulated NADH, and abolished FLC resistance. This indicates that ROS elevation alone cannot sustain resistance under severe mitochondrial impairment.\n SLA1<\/jats:italic>\n knockout compromised cell envelope integrity and attenuated in vivo virulence, revealing a fitness trade-off during antifungal adaptation. Clinical isolates exhibited a significant inverse correlation between\n SLA1<\/jats:italic>\n and\n CDR1<\/jats:italic>\n transcript levels.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study identifies SLA1 as a previously uncharacterized modulator of oxidative stress adaptation and azole susceptibility in\n C. auris<\/jats:italic>\n . Mitochondrial functional status governs the relationship between oxidative stress and azole resistance. The\n SLA1<\/jats:italic>\n -dependent axis promotes antifungal resistance at the expense of reduced virulence. These findings reveal a new mechanism of drug adaptation in\n C. auris<\/jats:italic>\n and point to a potential target for combating multidrug-resistant\n C. auris<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1948008","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:53:15Z","timestamp":1791352395000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SLA1 governs azole resistance in Candidozyma auris via mitochondrial ROS-driven efflux pump expression"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenhao","family":"Suo","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Center, General Hospital of Northern Theater Command","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Zhang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center (ChemBIC), Division of Immunology, Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Veterinary Medicine, Shenyang Agricultural University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The Second Affiliated Hospital of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, General Hospital of Northern Theater Command","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, General Hospital of Northern Theater Command","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Life and Health Science, Northeastern University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Center, General Hospital of Northern Theater Command","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"103859","DOI":"10.1016\/j.redox.2025.103859","article-title":"Mitochondrial membrane potential and compartmentalized signaling: calcium, ROS, and beyond","volume":"86","author":"Ahmed Selim","year":"2025","journal-title":"Redox Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/21505594.2022.2026037","article-title":"From environmental adaptation to host survival: attributes that mediate pathogenicity of Candida auris","volume":"13","author":"Allert","year":"2022","journal-title":"Virulence"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"128353","DOI":"10.1016\/j.micres.2025.128353","article-title":"The oxidative stress-related peroxiredoxin Tsa1b of Candidozyma (Candida) auris contributes to virulence and infection","volume":"302","author":"Areitio","year":"2026","journal-title":"Microbiol. 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