{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:28:25Z","timestamp":1790994505053,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Candida albicans (C. albicans) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly under conditions of dysbiosis or immunosuppression. Treatment remains challenging due to increasing multidrug resistance. This study investigates the in vitro antifungal potential of Viroelixir, a standardized polyphenol blend derived from green tea and pomegranate and enriched in catechins (including epigallocatechin gallate, EGCG), ellagitannins (notably punicalagin), ellagic acid, and flavonoids, with particular focus on its potential anti-virulence mechanisms. Methods: The effect of Viroelixir on C. albicans growth was assessed using MTT assay, optical density measurements, colony formation, carbohydrate quantification, and pH variation analysis. Biofilm formation, morphological transition, ROS production, necrosis, virulence gene expression, adhesion, and host immune responses were also evaluated. Results: Viroelixir significantly inhibited C. albicans growth and reduced colony formation compared with untreated controls. The formulation also inhibited biofilm formation and markedly reduced pseudohyphal development, reaching up to 94% reduction under specific treatment conditions. Flow cytometry analysis showed an increase in dead fungal cells, reaching approximately 88% following exposure to Viroelixir at the highest tested concentration. In addition, Viroelixir reduced the transcript levels of several virulence-associated genes, including SAP1\u2013SAP9 and EAP1. In epithelial cell co-culture models, pre-treatment of C. albicans with Viroelixir reduced fungal adhesion and attenuated epithelial inflammatory responses, including IL-6, IL-8, and hBD-2 production, and was associated with reduced activation of the TLR4-NF-\u03baB signaling pathway. Conclusions: These findings suggest that the antifungal and anti-virulence effects observed may be associated with the polyphenolic compounds present in the Viroelixir formulation, highlighting its potential as a promising in vitro antifungal candidate against C. albicans.<\/jats:p>","DOI":"10.3390\/antibiotics15040420","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Antifungal Activity of the Polyphenol Formulation Viroelixir Against Candida albicans"],"prefix":"10.3390","volume":"15","author":[{"given":"Manal","family":"Dahdah","sequence":"first","affiliation":[{"name":"GREB Research Group, Faculty of Dentistry, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Ettouil","sequence":"additional","affiliation":[{"name":"GREB Research Group, Faculty of Dentistry, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawraa","family":"Issa","sequence":"additional","affiliation":[{"name":"DREAM-CV Lab, Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Koussih","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Exp\u00e9rimentales, Universit\u00e9 de Saint-Boniface, Winnipeg, MB R2H 3B8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhlid H.","family":"Almutairi","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-8281","authenticated-orcid":false,"given":"Mahmoud","family":"Rouabhia","sequence":"additional","affiliation":[{"name":"GREB Research Group, Faculty of Dentistry, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-0377","authenticated-orcid":false,"given":"Abdelhabib","family":"Semlali","sequence":"additional","affiliation":[{"name":"GREB Research Group, Faculty of Dentistry, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106475","DOI":"10.1016\/j.rmed.2021.106475","article-title":"The Role of Oral Microbiome in Respiratory Health and Diseases","volume":"185","author":"Pathak","year":"2021","journal-title":"Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden Killers: Human Fungal Infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"876","DOI":"10.3201\/eid0808.020059","article-title":"Candida and Candidiasis","volume":"8","author":"Brandt","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.3402\/jom.v3i0.5771","article-title":"Pathogenesis and Treatment of Oral Candidosis","volume":"3","author":"Williams","year":"2011","journal-title":"J. Oral Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and Virulence of Candida albicans","volume":"13","author":"Lopes","year":"2022","journal-title":"Virulence"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans Pathogenicity Mechanisms","volume":"4","author":"Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref_8","first-page":"181","article-title":"Candida albicans and Cancer: Can This Yeast Induce Cancer Development or Progression?","volume":"42","author":"Rementeria","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.gde.2008.01.003","article-title":"Pathways Connecting Inflammation and Cancer","volume":"18","author":"Allavena","year":"2008","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1159\/000510979","article-title":"Oral Microbiota and Cancer Development","volume":"88","author":"Tuominen","year":"2020","journal-title":"Pathobiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1073\/pnas.78.3.1878","article-title":"Enhancement of Formation of the Esophageal Carcinogen Benzylmethylnitrosamine from Its Precursors by Candida albicans","volume":"78","author":"Hsia","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102451","DOI":"10.1016\/j.canep.2023.102451","article-title":"Candida Species as Potential Risk Factors for Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis","volume":"86","author":"Tasso","year":"2023","journal-title":"Cancer Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/omi.12064","article-title":"In Vitro Expression of Candida albicans Alcohol Dehydrogenase Genes Involved in Acetaldehyde Metabolism","volume":"30","author":"Bakri","year":"2015","journal-title":"Mol. Oral Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4103\/jomfp.jomfp_494_20","article-title":"Capacity of Candida Species to Produce Acetaldehyde at Various Concentrations of Alcohol","volume":"26","author":"Reddy","year":"2022","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11046-014-9749-1","article-title":"Candidiasis: Predisposing Factors, Prevention, Diagnosis and Alternative Treatment","volume":"177","author":"Martins","year":"2014","journal-title":"Mycopathologia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/1040841X.2020.1843400","article-title":"Candida albicans Biofilms and Polymicrobial Interactions","volume":"47","author":"Ponde","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1128\/EC.2.6.1266-1273.2003","article-title":"EAP1, a Candida albicans Gene Involved in Binding Human Epithelial Cells","volume":"2","author":"Li","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1128\/MMBR.67.3.400-428.2003","article-title":"Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis","volume":"67","author":"Naglik","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jdsr.2014.12.001","article-title":"Innate Immunity to Candida albicans","volume":"51","author":"Kiyoura","year":"2015","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tim.2007.10.012","article-title":"C-Type Lectin Receptors in Antifungal Immunity","volume":"16","author":"Willment","year":"2008","journal-title":"Trends Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1177\/0022034510368784","article-title":"Epithelial Cells and Innate Antifungal Defense","volume":"89","author":"Weindl","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1128\/JCM.42.3.1024-1029.2004","article-title":"Human Beta-Defensins 2 and 3 Demonstrate Strain-Selective Activity against Oral Microorganisms","volume":"42","author":"Joly","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1128\/AAC.00478-06","article-title":"Human Beta-Defensins Kill Candida albicans in an Energy-Dependent and Salt-Sensitive Manner without Causing Membrane Disruption","volume":"51","author":"Vylkova","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.4049\/jimmunol.171.6.3047","article-title":"Candida albicans Induces Selectively Transcriptional Activation of Cyclooxygenase-2 in HeLa Cells: Pivotal Roles of Toll-like Receptors, P38 Mitogen-Activated Protein Kinase, and NF-Kappa B","volume":"171","author":"Deva","year":"2003","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1469-0691.2008.01984.x","article-title":"Liposomal Amphotericin B: What Is Its Role in 2008?","volume":"14","author":"Lanternier","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gonzalez-Jimenez, I., Perlin, D.S., and Shor, E. (2023). Reactive Oxidant Species Induced by Antifungal Drugs: Identity, Origins, Functions, and Connection to Stress-Induced Cell Death. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1276406"},{"key":"ref_27","first-page":"149","article-title":"Clinical Hepatotoxicity Associated with Antifungal Agents","volume":"16","author":"Kyriakidis","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.peptides.2011.01.020","article-title":"Antimicrobial Decapeptide KSL-W Attenuates Candida albicans Virulence by Modulating Its Effects on Toll-like Receptor, Human \u03b2-Defensin, and Cytokine Expression by Engineered Human Oral Mucosa","volume":"32","author":"Semlali","year":"2011","journal-title":"Peptides"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1055\/s-0042-104509","article-title":"Innovation in Phytotherapy: Is a New Regulation the Feasible Perspective in Europe?","volume":"82","author":"Minghetti","year":"2016","journal-title":"Planta Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1590\/1806-9282.64.09.765","article-title":"Phytotherapy: Yesterday, Today, and Forever?","volume":"64","author":"Lopes","year":"2018","journal-title":"Rev. Assoc. Medica Bras."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9197","DOI":"10.1021\/jf901466c","article-title":"Environmental Conditions Affect the Color, Taste, and Antioxidant Capacity of 11 Pomegranate Accessions\u2019 Fruits","volume":"57","author":"Schwartz","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sharma, P., McClees, S.F., and Afaq, F. (2017). Pomegranate for Prevention and Treatment of Cancer: An Update. Molecules, 22.","DOI":"10.3390\/molecules22010177"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.2174\/1871520611313080003","article-title":"Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities","volume":"13","author":"Syed","year":"2013","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"von Eckardstein, A. (2005). Dietary Antioxidants and Paraoxonases Against LDL Oxidation and Atherosclerosis Development. Atherosclerosis: Diet and Drugs, Springer. Handbook of Experimental Pharmacology.","DOI":"10.1007\/3-540-27661-0"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"938475","DOI":"10.1155\/2015\/938475","article-title":"Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy","volume":"2015","author":"Turrini","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.jnutbio.2005.01.006","article-title":"In Vitro Antiproliferative, Apoptotic and Antioxidant Activities of Punicalagin, Ellagic Acid and a Total Pomegranate Tannin Extract Are Enhanced in Combination with Other Polyphenols as Found in Pomegranate Juice","volume":"16","author":"Seeram","year":"2005","journal-title":"J. Nutr. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.resmic.2010.05.002","article-title":"Potent Antifungal Activity of Extracts and Pure Compound Isolated from Pomegranate Peels and Synergism with Fluconazole against Candida albicans","volume":"161","author":"Endo","year":"2010","journal-title":"Res. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2174\/1871523015666160915154443","article-title":"Anti-Inflammatory Action of Green Tea","volume":"15","author":"Ohishi","year":"2016","journal-title":"Anti-Inflamm. Anti-Allergy Agents Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Musial, C., Kuban-Jankowska, A., and Gorska-Ponikowska, M. (2020). Beneficial Properties of Green Tea Catechins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051744"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, Y., and Zhang, T. (2019). Antimicrobial Activities of Tea Polyphenol on Phytopathogens: A Review. Molecules, 24.","DOI":"10.3390\/molecules24040816"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dahdah, M., Nimbarte, V.D., Rouabhia, M., Ettouil, Y., Issa, H., Koussih, L., Almutairi, M.H., and Semlali, A. (2026). Mechanistic Insights into the Anti-Virulence Effects of Viroelixir, a Phenolic Blend from Green Tea and Pomegranate, on Streptococcus Mutans. Antibiotics, 15.","DOI":"10.3390\/antibiotics15040406"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e13810","DOI":"10.1016\/j.heliyon.2023.e13810","article-title":"Phytochemicals as Alternative Fungicides for Controlling Plant Diseases: A Comprehensive Review of Their Efficacy, Commercial Representatives, Advantages, Challenges for Adoption, and Possible Solutions","volume":"9","author":"Deresa","year":"2023","journal-title":"Heliyon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/jac\/dkh046","article-title":"Multiple Effects of Green Tea Catechin on the Antifungal Activity of Antimycotics against Candida albicans","volume":"53","author":"Hirasawa","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e1690747","DOI":"10.1155\/2018\/1690747","article-title":"Green Tea Polyphenols and Padma Hepaten Inhibit Candida albicans Biofilm Formation","volume":"2018","author":"Farkash","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ijfoodmicro.2009.07.002","article-title":"Antimicrobial Activity of Pomegranate (Punica granatum L.) Fruit Peels","volume":"134","year":"2009","journal-title":"Int. J. Food Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jep.2009.06.025","article-title":"Antiplasmodial Activity of Punica granatum L. Fruit Rind","volume":"125","author":"Galli","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.phymed.2004.11.009","article-title":"Antibacterial Properties of Tropical Plants from Puerto Rico","volume":"13","author":"Capriles","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12941-014-0032-6","article-title":"Antifungal Activity of Pomegranate Peel Extract and Isolated Compound Punicalagin against Dermatophytes","volume":"13","author":"Foss","year":"2014","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/iub.2476","article-title":"Naringin-Generated ROS Promotes Mitochondria-Mediated Apoptosis in Candida albicans","volume":"73","author":"Kim","year":"2021","journal-title":"IUBMB Life"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s11046-016-9992-8","article-title":"Modulation of Candida albicans Biofilm by Different Carbon Sources","volume":"181","author":"Pemmaraju","year":"2016","journal-title":"Mycopathologia"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Van Ende, M., Wijnants, S., and Van Dijck, P. (2019). Sugar Sensing and Signaling in Candida albicans and Candida Glabrata. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00099"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Atriwal, T., Azeem, K., Husain, F.M., Hussain, A., Khan, M.N., Alajmi, M.F., and Abid, M. (2021). Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.638609"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.micinf.2016.01.002","article-title":"Candida albicans Biofilms: Development, Regulation, and Molecular Mechanisms","volume":"18","author":"Gulati","year":"2016","journal-title":"Microbes Infect."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mukaremera, L., Lee, K.K., Mora-Montes, H.M., and Gow, N.A.R. (2017). Candida albicans Yeast, Pseudohyphal, and Hyphal Morphogenesis Differentially Affects Immune Recognition. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00629"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Talapko, J., Juzba\u0161i\u0107, M., Matijevi\u0107, T., Pustijanac, E., Beki\u0107, S., Kotris, I., and \u0160krlec, I. (2021). Candida albicans\u2014The Virulence Factors and Clinical Manifestations of Infection. J. Fungi, 7.","DOI":"10.3390\/jof7020079"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tazi, N., Pigeon, X., Mbuyi-Boisvert, J.M., Giret, S., B\u00e9land, F., and Rouabhia, M. (2021). Effect of Cannabis Smoke Condensate on C. albicans Growth and Biofilm Formation. Microorganisms, 9.","DOI":"10.3390\/microorganisms9112348"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s12602-020-09685-0","article-title":"Effect of Dermaseptin S4 on C. albicans Growth and EAP1 and HWP1 Gene Expression","volume":"13","author":"Samot","year":"2021","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1128\/IAI.00282-15","article-title":"Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis","volume":"83","author":"Kumar","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11046-009-9232-6","article-title":"Effects of Antifungal Agents in Sap Activity of Candida albicans Isolates","volume":"169","author":"Costa","year":"2010","journal-title":"Mycopathologia"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Alves, R., Barata-Antunes, C., Casal, M., Brown, A.J.P., Van Dijck, P., and Paiva, S. (2020). Adapting to Survive: How Candida Overcomes Host-Imposed Constraints during Human Colonization. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008478"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1342","DOI":"10.1002\/mbo3.1342","article-title":"Assessing pH-Dependent Activities of Virulence Factors Secreted by Candida albicans","volume":"12","author":"Eraso","year":"2023","journal-title":"MicrobiologyOpen"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/jb\/mvr073","article-title":"Comprehensive Characterization of Secreted Aspartic Proteases Encoded by a Virulence Gene Family in Candida albicans","volume":"150","author":"Aoki","year":"2011","journal-title":"J. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10766","DOI":"10.3390\/ijms150610766","article-title":"Role of Candida albicans-Secreted Aspartyl Proteinases (Saps) in Severe Early Childhood Caries","volume":"15","author":"Li","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000204911","article-title":"Acid Production by Oral Strains of Candida albicans and Lactobacilli","volume":"43","author":"Klinke","year":"2009","journal-title":"Caries Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00055-11","DOI":"10.1128\/mBio.00055-11","article-title":"The Fungal Pathogen Candida albicans Autoinduces Hyphal Morphogenesis by Raising Extracellular pH","volume":"2","author":"Vylkova","year":"2011","journal-title":"mBio"},{"key":"ref_66","first-page":"119","article-title":"Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease","volume":"7","author":"Dale","year":"2005","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Fusco, A., Savio, V., Donniacuo, M., Perfetto, B., and Donnarumma, G. (2021). Antimicrobial Peptides Human Beta-Defensin-2 and -3 Protect the Gut During Candida albicans Infections Enhancing the Intestinal Barrier Integrity: In Vitro Study. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.666900"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"963156","DOI":"10.1155\/2014\/963156","article-title":"Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses","volume":"2014","author":"Alanazi","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1099\/mic.0.2008\/022525-0","article-title":"Secreted Aspartic Proteases Are Not Required for Invasion of Reconstituted Human Epithelia by Candida albicans","volume":"154","author":"Lermann","year":"2008","journal-title":"Microbiology"},{"key":"ref_70","first-page":"163","article-title":"Characteristics of Biofilm Formation by Candida albicans","volume":"18","author":"Ramage","year":"2001","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.4049\/jimmunol.1203239","article-title":"\u03b2-Defensin 1 Plays a Role in Acute Mucosal Defense against Candida albicans","volume":"194","author":"Tomalka","year":"2015","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cellimm.2015.09.010","article-title":"Anti-Inflammatory Effect of Curcumin on Mast Cell-Mediated Allergic Responses in Ovalbumin-Induced Allergic Rhinitis Mouse","volume":"298","author":"Zhang","year":"2015","journal-title":"Cell. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2148","DOI":"10.7717\/peerj.2148","article-title":"In Vitro Evaluation of Antifungal Activity of Monolaurin against Candida albicans Biofilms","volume":"4","author":"Seleem","year":"2016","journal-title":"PeerJ"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s12275-024-00134-z","article-title":"Licochalcone A Protects Vaginal Epithelial Cells Against Candida albicans Infection Via the TLR4\/NF-\u03baB Signaling Pathway","volume":"62","author":"Li","year":"2024","journal-title":"J. Microbiol."},{"key":"ref_75","first-page":"3664","article-title":"Human Epithelial Cells Establish Direct Antifungal Defense through TLR4-Mediated Signaling","volume":"117","author":"Weindl","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.chom.2010.08.002","article-title":"A Biphasic Innate Immune MAPK Response Discriminates between the Yeast and Hyphal Forms of Candida albicans in Epithelial Cells","volume":"8","author":"Moyes","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3109\/13693781003621575","article-title":"Variable Recognition of Candida albicans Strains by TLR4 and Lectin Recognition Receptors","volume":"48","author":"Netea","year":"2010","journal-title":"Med. Mycol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00018-020-03656-y","article-title":"TLR4 and CD14 Trafficking and Its Influence on LPS-Induced pro-Inflammatory Signaling","volume":"78","author":"Ciesielska","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.immuni.2015.10.008","article-title":"Mechanisms of Toll-like Receptor 4 Endocytosis Reveal a Common Immune-Evasion Strategy Used by Pathogenic and Commensal Bacteria","volume":"43","author":"Tan","year":"2015","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/ni1569","article-title":"TRAM Couples Endocytosis of Toll-like Receptor 4 to the Induction of Interferon-\u03b2","volume":"9","author":"Kagan","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.immuni.2016.07.010","article-title":"ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination","volume":"45","author":"Akbar","year":"2016","journal-title":"Immunity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/jam.13745","article-title":"Dermaseptin-S1 Decreases Candida albicans Growth, Biofilm Formation and the Expression of Hyphal Wall Protein 1 and Aspartic Protease Genes","volume":"125","author":"Belmadani","year":"2018","journal-title":"J. Appl. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Mezni, G., Issa, H., Dahdah, M., Poulin, A., Da\u00efch, A., Alamri, A., Rouabhia, M., and Semlali, A. (2025). New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms. Antibiotics, 14.","DOI":"10.3390\/antibiotics14050495"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1128\/AAC.48.7.2350-2354.2004","article-title":"Defined Anaerobic Growth Medium for Studying Candida albicans Basic Biology and Resistance to Eight Antifungal Drugs","volume":"48","author":"Dumitru","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Theberge, S., Semlali, A., Alamri, A., Leung, K.P., and Rouabhia, M.C. (2013). albicans Growth, Transition, Biofilm Formation, and Gene Expression Modulation by Antimicrobial Decapeptide KSL-W. BMC Microbiol., 13.","DOI":"10.1186\/1471-2180-13-246"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1021\/ac60111a017","article-title":"Colorimetric Method for Determination of Sugars and Related Substances","volume":"28","author":"DuBois","year":"1956","journal-title":"Anal. Chem."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/4\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:38:34Z","timestamp":1776789514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/4\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":86,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antibiotics15040420"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15040420","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}