{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:49:54Z","timestamp":1793022594417,"version":"4.5.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Nakaseomyces glabratus<\/jats:italic>\n                      exhibits intrinsic tolerance to azole antifungals, frequently mediated by gain-of-function (GOF) mutations in the transcription factor\n                      <jats:italic toggle=\"yes\">CgPDR1<\/jats:italic>\n                      . While efflux-mediated resistance is well established, its potential interaction with oxidative stress\u2013dependent cell death pathways in biofilms remains insufficiently characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      Fifteen clinical isolates (susceptible,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5; resistant,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 10) were analyzed under planktonic and biofilm conditions. Antifungal susceptibility to itraconazole (0.03\u201332 \u00b5g\/mL) was determined, while apoptosis and intracellular reactive oxygen species (ROS) were quantified using Annexin V\/PI staining and fluorescence-based assays, respectively. The role of oxidative stress was evaluated using ascorbic acid co-treatment.\n                      <jats:italic toggle=\"yes\">CgPDR1<\/jats:italic>\n                      mutations were identified by sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Resistant isolates exhibited significantly elevated minimum inhibitory concentration (MIC) values (up to 32 \u00b5g\/mL) and a high prevalence of\n                      <jats:italic toggle=\"yes\">CgPDR1<\/jats:italic>\n                      mutations (K274N: 100%; D1082G: 30%; S343F: 10%). Itraconazole induced a marked increase in ROS production and apoptosis in susceptible biofilms (Annexin V\n                      <jats:sup>+<\/jats:sup>\n                      \u2248 70%), whereas resistant isolates demonstrated attenuated ROS generation and reduced apoptosis (\u224810%,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.01). Although ascorbic acid significantly decreased ROS levels in susceptible isolates, it did not alter MIC values or restore antifungal susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">CgPDR1<\/jats:italic>\n                      GOF mutations are associated with a coordinated resistance phenotype in\n                      <jats:italic toggle=\"yes\">N. glabratus<\/jats:italic>\n                      biofilms, characterized by enhanced drug tolerance and reduced ROS-mediated apoptosis. These findings support a multifactorial resistance model and identify K274N as a potential population-specific biomarker.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10766294261470531","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:57:26Z","timestamp":1784210246000},"page":"536-543","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Itraconazole-Induced Apoptosis in\n                    <i>Candida glabrata<\/i>\n                    (\n                    <i>Nakaseomyces glabratus<\/i>\n                    ) Biofilms: Role of ROS and\n                    <i>CgPDR<\/i>\n                    1 Mutations (K274N, D1082G, and S343F) in Resistant Clinical Isolates"],"prefix":"10.1177","volume":"32","author":[{"given":"Farnaz","family":"Valizadeh","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran."},{"name":"Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-4644","authenticated-orcid":false,"given":"Mahsa","family":"Fattahi","sequence":"additional","affiliation":[{"name":"Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran."},{"name":"Children\u2019s Medical Center Hospital, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ensieh","family":"Lotfali","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Motamed","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13725"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14988"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1872213X13666191026090713"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2007.00262.x"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.1998.00380.x"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycmed.2023.101234"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010412"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03088-22"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38940-5"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00324-22"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008358"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9010050"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S362635"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1M165"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-032304841-5.50055-8"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2013.06.010"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8030225"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00102-22"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02380-20"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00045-1"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18932"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdin.2022.04.003"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.09.067"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.11.020"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011164"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2023.03.007"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01422-22"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcsw.2023.100105"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9020248"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2024.102424"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00960-9"},{"key":"e_1_3_2_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1276406"}],"container-title":["Microbial 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