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This study evaluates and compares the antifungal efficacy of biologically synthesized zinc oxide nanoparticles (ZnO-NP-B) and chemically synthesized ZnO nanoparticles (ZnO-NP-C1 and ZnO-NP-C2), developed using the dry\u2013wet chemical method and sol\u2013gel method, respectively. ZnO-NP-B was synthesized using <jats:italic>Lactobacillus gasseri<\/jats:italic>. The nanoparticles were characterized for size, charge, and morphology using Particle Size Analyzer, photon correlation spectroscopy with a 90 Plus Zetasizer, and scanning electron microscopy (SEM), respectively<jats:bold>.<\/jats:bold> The antifungal activity was assessed through minimum inhibitory concentration (MIC<jats:sub>50<\/jats:sub>) determination, biofilm inhibition assays by XTT assay, and gene expression analysis. ZnO-NP-C1 exhibited the highest antifungal activity against <jats:italic>C. auris<\/jats:italic> planktonic cells, with a MIC<jats:sub>50<\/jats:sub> value of 61.9\u2009\u00b1\u20093.3\u00a0\u00b5g\/ml, followed by ZnO-NP-C2 (151\u2009\u00b1\u20097.83\u00a0\u00b5g\/ml), whereas ZnO-NP-B showed limited efficacy (MIC<jats:sub>50<\/jats:sub>\u2009=\u20091\u00a0mg\/ml). Chemically synthesized ZnO-NPs, particularly ZnO-NP-C2, did not induce overexpression of resistance genes (<jats:italic>CDR1, MDR1, ERG2, ERG11, FKS1, CHS1<\/jats:italic>), whereas ZnO-NP-B triggered their upregulation, potentially promoting resistance. ZnO-NP-C1 was the most effective in preventing biofilm formation, reducing <jats:italic>C. auris<\/jats:italic> adhesion by 67.9\u2009\u00b1\u20092.35% at 150\u00a0\u00b5g\/ml, while ZnO-NP-B exhibited negligible inhibition. Gene expression analysis further confirmed that ZnO-NP-C1 significantly downregulated adhesive genes (<jats:italic>ALS5, IFF4, CSA1<\/jats:italic>) by up to 0.37\u2009\u00b1\u20090.006, 0.043\u2009\u00b1\u20090.002, and 0.06\u2009\u00b1\u20090.0004, respectively. These findings highlight the potential of ZnO-NP-C1 as a promising antifungal agent for preventing <jats:italic>C. auris<\/jats:italic> biofilms, emphasizing the critical role of synthesis methods in optimizing nanoparticle properties for antifungal applications.<\/jats:p>","DOI":"10.1007\/s10534-025-00678-6","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T11:07:41Z","timestamp":1743505661000},"page":"817-830","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparative evaluation of biologically and chemically synthesized zinc oxide nanoparticles for preventing Candida auris biofilm"],"prefix":"10.1007","volume":"38","author":[{"given":"Bahgat","family":"Fayed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda S.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha E.","family":"Reda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"678_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27041236","author":"HM Abdelmigid","year":"2022","unstructured":"Abdelmigid HM, Hussien NA, Alyamani AA, Morsi MM, AlSufyani NM, Kadi HA (2022) Green synthesis of zinc oxide nanoparticles using pomegranate fruit peel and solid coffee grounds vs. chemical method of synthesis, with their biocompatibility and antibacterial properties investigation. 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