{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:26Z","timestamp":1791521426868,"version":"4.3.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173429"],"award-info":[{"award-number":["82173429"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Alcohol dehydrogenases (ADHs) participate in fungal carbon metabolism and redox homeostasis, but the contribution of\n ADH2<\/jats:italic>\n to virulence-associated phenotypes and fluconazole response in\n Candida albicans<\/jats:italic>\n (\n C. albicans<\/jats:italic>\n ) remains incompletely defined.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n An\n ADH2<\/jats:italic>\n deletion mutant,\n adh2\u0394\/\u0394<\/jats:italic>\n , was generated in a SC5314 genetic background. Growth kinetics, adhesion, filamentous development, biofilm metabolic activity, cell surface hydrophobicity, intracellular ATP, reactive oxygen species, mitochondrial membrane potential, NAD\n +<\/jats:sup>\n \/NADH ratio, selected glucose-metabolism-related transcript levels, fluconazole response, and\n in vivo<\/jats:italic>\n infection burden were evaluated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n adh2\u0394\/\u0394<\/jats:italic>\n mutant displayed modestly altered growth kinetics and showed a shorter doubling time than SC5314. However, qualitative assays showed reduced adhesion and filamentous development, accompanied by decreased expression of\n ALS1<\/jats:italic>\n ,\n ALS3<\/jats:italic>\n , and\n HWP1<\/jats:italic>\n . The mutant displayed increased biofilm metabolic activity but decreased cell surface hydrophobicity, together with increased\n CSH1<\/jats:italic>\n expression. Metabolic analyses showed reduced ATP levels and basal intracellular ROS-sensitive fluorescence, together with an increased NAD\n +<\/jats:sup>\n \/NADH ratio and elevated mitochondrial membrane potential. Among selected glucose-metabolism-related genes,\n HXK1<\/jats:italic>\n was significantly upregulated after correction for multiple testing, whereas\n CDC19<\/jats:italic>\n ,\n PGI1<\/jats:italic>\n , and\n PGK1<\/jats:italic>\n were not significantly altered. The\n adh2\u0394\/\u0394<\/jats:italic>\n mutant showed a two-fold increase in fluconazole MIC and stronger growth under FLCZ stress, accompanied by increased\n ERG11<\/jats:italic>\n transcript levels, whereas\n MDR1<\/jats:italic>\n ,\n CDR1<\/jats:italic>\n , and\n CDR2<\/jats:italic>\n were not significantly altered after correction for multiple testing;\n ADH1<\/jats:italic>\n was also unchanged. In mice,\n adh2\u0394\/\u0394<\/jats:italic>\n infection resulted in higher renal fungal burden and higher residual renal fungal burden after fluconazole treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n These findings define an\n ADH2<\/jats:italic>\n deletion-associated phenotypic and metabolic\/redox state and provide a hypothesis-generating framework for exploring its association with reduced fluconazole susceptibility in\n C. albicans<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1911561","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:16Z","timestamp":1791519976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic and metabolic characterization of an ADH2 deletion mutant associated with reduced fluconazole susceptibility in Candida albicans"],"prefix":"10.3389","volume":"16","author":[{"given":"Chunjiao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Su","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"An","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine","place":["Shanghai, China"]},{"name":"Laboratory of Pathogen-Host Interaction (Tongji University), Ministry of Education","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Center of Infectious Skin Diseases, Shanghai Skin Disease Hospital, Tongji University School of Medicine","place":["Shanghai, China"]},{"name":"Laboratory of Pathogen-Host Interaction (Tongji University), Ministry of Education","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1111\/jop.12193","article-title":"Detection of candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples","volume":"43","author":"Bakri","year":"2014","journal-title":"J. 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