{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:22:48Z","timestamp":1771935768830,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"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. Cell. Infect. Microbiol."],"abstract":"\n Objective<\/jats:title>\n \n To verify the causal relationship between specific mutations in the\n ERG11<\/jats:italic>\n and\n FKS1<\/jats:italic>\n genes and antifungal drug resistance in clinical isolates of\n Diutina catenulata<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Recombinant plasmids expressing mutant alleles of\n ERG11<\/jats:italic>\n (F126L, K143R) or\n FKS1<\/jats:italic>\n (F621I, S1123G, I1348S, and the triple mutant S625L\/S1123G\/F1354L) were constructed and functionally validated in a\n Saccharomyces cerevisiae<\/jats:italic>\n W303-1a model. Susceptibility testing was performed under different nutrient conditions (SD-Ura and YPD). Molecular docking analysis was conducted to elucidate the structural mechanisms of resistance.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Functional validation in\n S. cerevisiae<\/jats:italic>\n confirmed that both\n ERG11<\/jats:italic>\n and\n FKS1<\/jats:italic>\n mutations conferred resistance in a nutrient-dependent manner. The\n ERG11<\/jats:italic>\n -F126L mutation increased the fluconazole MIC by 21-fold in SD-Ura compared to YPD.\n FKS1<\/jats:italic>\n mutations led to 1.4 to 2-fold increases in echinocandin MICs. Molecular docking revealed the mechanistic bases:\n ERG11<\/jats:italic>\n -F126L expanded the ligand-binding cavity (\u0394\u0394G +1.2 kcal\/mol),\n FKS1<\/jats:italic>\n -F621I disrupted hydrophobic interactions, and compound mutations synergistically perturbed ATP-binding domains.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Specific mutations in\n ERG11<\/jats:italic>\n (F126L, K143R) and\n FKS1<\/jats:italic>\n (F621I and hotspot variants) are the primary drivers of the pronounced antifungal resistance observed in Chinese\n D. catenulata<\/jats:italic>\n strains, with resistance phenotypes being modulated by nutrient availability.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1776442","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:33:33Z","timestamp":1771310013000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding resistance in Diutina catenulata by validating clinically relevant Erg11\/Fks1 mutations"],"prefix":"10.3389","volume":"16","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Hebei Key Laboratory of Pathogenic Mechanisms and Diagnosis & Treatment Technologies for Lung Microbiome, The First Affiliated Hospital of Hebei North University","place":["Zhangjiakou, Hebei, China"]},{"name":"Hebei Key Laboratory of Pathogens and Epidemiology of Infectious Diseases, Hebei Provincial Center for Disease Control and Prevention","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Pathogenic Mechanisms and Diagnosis & Treatment Technologies for Lung Microbiome, The First Affiliated Hospital of Hebei North University","place":["Zhangjiakou, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Hua","family":"He","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Pathogens and Epidemiology of Infectious Diseases, Hebei Provincial Center for Disease Control and Prevention","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Chun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Pathogens and Epidemiology of Infectious Diseases, Hebei Provincial Center for Disease Control and Prevention","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1007\/s00284-024-03854-y","article-title":"A Cluster of Diutina catenulata Funguria in Patients with Coronavirus Disease 2019 (COVID-19) Hospitalized in a Tertiary Reference Hospital from Rio de Janeiro, Brazil","volume":"81","author":"Almeida-Paes","year":"2024","journal-title":"Curr. 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