{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:10:47Z","timestamp":1778044247342,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Vulvovaginal candidiasis (VVC) is a common gynecological infection, with Pichia kudriavzevii emerging as a significant pathogen due to its intrinsic fluconazole resistance and biofilm-forming capacity. This study investigates the antifungal efficacy and mechanisms of tannic acid (TA) against P. kudriavzevii, as well as its potential to reverse azole resistance across multiple Candida species with distinct resistance profiles. TA significantly inhibited P. kudriavzevii growth, surface colonization, and virulence gene expression at 3 \u03bcg\/mL. Mechanistically, TA protected the human vaginal epithelial cell line VK2\/E6E7 by reducing ROS levels, restoring mitochondrial membrane potential, and suppressing IL-1\u03b2 and IL-18 release through modulation of the NLRP3-Caspase1-ASC axis. Furthermore, TA demonstrated synergistic activity when combined with azoles against five clinically azole-resistant Candida isolates spanning three Candida species with distinct resistance mechanisms: P. kudriavzevii (intrinsic), C. albicans (acquired), and N. glabrata (FKS-mediated). This study highlights TA as a promising natural therapeutic agent for P. kudriavzevii infections and offers a novel strategy for combating multidrug-resistant Candida through combination therapy.<\/jats:p>","DOI":"10.3390\/pathogens15050464","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:40:12Z","timestamp":1777981212000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Mechanism of Tannic Acid Against Pichia kudriavzevii in the VK2\/E6E7 Vaginal Epithelial Cell Line and Its Synergy with Azoles on Drug-Resistant Candida Species"],"prefix":"10.3390","volume":"15","author":[{"given":"Meng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Medical Mycology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"},{"name":"Jiangsu Provincial Key Laboratory of Dermatology, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Ren","sequence":"additional","affiliation":[{"name":"Centers for Pharmaceutical Preparations, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"},{"name":"Jiangsu Provincial Key Laboratory of Dermatology, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-2513","authenticated-orcid":false,"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0291-2949","authenticated-orcid":false,"given":"Weida","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"},{"name":"Jiangsu Provincial Key Laboratory of Dermatology, Nanjing 210042, China"},{"name":"Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 210008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jiangsu Province Hospital of Traditional Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"She","sequence":"additional","affiliation":[{"name":"Department of Medical Mycology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China"},{"name":"Jiangsu Provincial Key Laboratory of Dermatology, Nanjing 210042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Doi, A.M., Pignatari, A.C., Edmond, M.B., Marra, A.R., Camargo, L.F., Siqueira, R.A., da Mota, V.P., and Colombo, A.L. 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