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This study tested four proteins\/peptides\ue5f8histatin 3 (His3), histatin 5 (His5), DR9-RR14, and RR14\ue5f8on these mixed biofilms grown on acrylic resin. Using previously determined biofilm inhibitory concentrations (BIC-2), their effects on biofilm viability, ECM components (proteins, extracellular DNA, and polysaccharides), and biofilm structure were assessed. His3 and His5 were the most effective, reducing biofilm cells by 46 and 41% and significantly decreasing ECM components. DR9-RR14 and RR14 had moderate effects. Imaging confirmed that His3 and His5 disrupted the biofilm structure. Cytotoxicity tests showed that all proteins\/peptides were safe for gingival fibroblasts. Among the proteins\/peptides evaluated, His3 showed the highest effectiveness, making it a promising candidate for preventing biofilm formation and ECM maturation, suggesting its potential use in treating denture stomatitis.<\/jats:p>","DOI":"10.1021\/acsomega.5c02108","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T11:03:44Z","timestamp":1750244624000},"page":"27011-27022","source":"Crossref","is-referenced-by-count":3,"title":["Unlocking Histatin\nPotential against\n                    <i>Candida albicans<\/i>\n                    and\n                    <i>Streptococcus\nmutans<\/i>\n                    Biofilms: Targeting the Extracellular Matrix\nWhile Preserving Oral Cell Integrity"],"prefix":"10.1021","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-9715","authenticated-orcid":true,"given":"Luana\nMendonc\u0327a","family":"Dias","sequence":"first","affiliation":[{"name":"University of Saskatchewan (USASK) , , 105 Wiggins Road , , ,","place":["Saskatoon, SK, Canada, S7N 5E4"]},{"name":"Universidade Estadual Paulista \u201cJu\u0301lio de Mesquita Filho\u201d, Faculdade de Odontologia de Araraquara , , Rua Humaita\u0301, 1680 , , ,","place":["Araraquara, SP, Brazil, 14803-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2108-4656","authenticated-orcid":true,"given":"Lina M.","family":"Marin","sequence":"additional","affiliation":[{"name":"University of Saskatchewan (USASK) , , 105 Wiggins Road , , ,","place":["Saskatoon, SK, Canada, S7N 5E4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-1994","authenticated-orcid":true,"given":"Ana Claudia","family":"Pavarina","sequence":"additional","affiliation":[{"name":"Universidade Estadual Paulista \u201cJu\u0301lio de Mesquita Filho\u201d, Faculdade de Odontologia de Araraquara , , Rua Humaita\u0301, 1680 , , ,","place":["Araraquara, SP, Brazil, 14803-901"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-3658","authenticated-orcid":true,"given":"Walter L.","family":"Siqueira","sequence":"additional","affiliation":[{"name":"University of Saskatchewan (USASK) , , 105 Wiggins Road , , ,","place":["Saskatoon, SK, Canada, S7N 5E4"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"issue":"2","key":"2026081811264266800_cit1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1177\/10454411940050020101","article-title":"Candida and Oral Candidosis: A Review","volume":"5","author":"Scully","year":"1994","journal-title":"Critical Reviews in Oral Biology & Medicine"},{"issue":"3","key":"2026081811264266800_cit2","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/jopr.12198","article-title":"A Multispecies\nProbiotic Reduces Oral Candida Colonization in Denture\nWearers","volume":"24","author":"Ishikawa","year":"2015","journal-title":"Journal of Prosthodontics"},{"issue":"12","key":"2026081811264266800_cit3","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1016\/j.archoralbio.2007.06.007","article-title":"Characteristics of Dual Species Candida\nBiofilms on Denture Acrylic Surfaces","volume":"52","author":"Thein","year":"2007","journal-title":"Arch Oral\nBiol."},{"issue":"9","key":"2026081811264266800_cit4","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1177\/0022034515592859","article-title":"Binding Force\nDynamics of Streptococcus Mutans-Glucosyltransferase B to Candida\nAlbicans","volume":"94","author":"Hwang","year":"2015","journal-title":"J. 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Agents Chemother."},{"issue":"3","key":"2026081811264266800_cit28","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.tim.2017.09.008","article-title":"Oral Biofilms: Pathogens,\nMatrix, and Polymicrobial Interactions in Microenvironments","volume":"26","author":"Bowen","year":"2018","journal-title":"Trends Microbiol"},{"key":"2026081811264266800_cit29","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.actbio.2020.08.032","article-title":"Dual Antibacterial\nDrug-Loaded Nanoparticles Synergistically\nImprove Treatment of Streptococcus Mutans Biofilms","volume":"115","author":"Sims","year":"2020","journal-title":"Acta Biomater"},{"issue":"1","key":"2026081811264266800_cit30","doi-asserted-by":"publisher","first-page":"1476644","DOI":"10.1080\/20002297.2018.1476644","article-title":"Fluconazole Impacts\nthe Extracellular Matrix of Fluconazole-Susceptible and -Resistant Candida Albicans and Candida Glabrata Biofilms","volume":"10","author":"Panariello","year":"2018","journal-title":"J. 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Macromol."},{"issue":"4265","key":"2026081811264266800_cit39","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/168167a0","article-title":"A Colorimetric\nMethod for the Determination of Sugars","volume":"168","author":"DUBOIS","year":"1951","journal-title":"Nature"},{"issue":"12","key":"2026081811264266800_cit40","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1128\/JB.01649-09","article-title":"Exopolysaccharides\nProduced by Streptococcus Mutans Glucosyltransferases Modulate the\nEstablishment of Microcolonies within Multispecies Biofilms","volume":"192","author":"Koo","year":"2010","journal-title":"J. Bacteriol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.5c02108","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/10\/25\/27011\/40836894\/ao5c02108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/10\/25\/27011\/40836894\/ao5c02108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:25:27Z","timestamp":1787070327000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/10\/25\/27011\/3654659\/Unlocking-Histatin-Potential-against-Candida"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":40,"journal-issue":{"issue":"25","published-online":{"date-parts":[[2025,6,18]]},"published-print":{"date-parts":[[2025,7,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.5c02108","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]}}}