{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:16:32Z","timestamp":1792440992013,"version":"4.5.0"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Polymicrobial infections involving <jats:italic>Candida albicans<\/jats:italic> and <jats:italic>Porphyromonas gingivalis<\/jats:italic> represent a significant challenge in maintaining epithelial barrier integrity. This study explores their synergistic effects on epithelial cells using an air-liquid interface (ALI) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mixed-species biofilms were developed and analyzed for their impact on epithelial permeability and tight junction proteins. The effects of biofilm supernatants on IL-8 secretion and oxidative stress markers were also evaluated. The role of <jats:italic>P. gingivalis<\/jats:italic> proteases was assessed using a gingipain-null mutant (\u0394K\u0394RAB) compared to the wild-type strain (W83). Survival experiments were conducted using <jats:italic>Galleria mellonella<\/jats:italic> larvae to examine the pathogenicity of dual-species biofilms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mixed-species biofilms significantly increased epithelial permeability and disrupted tight junction proteins, as evidenced by reduced levels of ZO-1 and E-cadherin. These changes were accompanied by oxidative stress, characterized by decreased HO-1 expression and enhanced Bax\/Bcl-xL ratios, indicating increased pro-apoptotic activity. Supernatants from dual-species biofilms demonstrated a pronounced effect on epithelial cells, modulating IL-8 secretion and exacerbating oxidative damage. <jats:italic>C. albicans<\/jats:italic> was identified as the dominant driver of pro-inflammatory responses, while <jats:italic>P. gingivalis<\/jats:italic> contributed through immune modulation and enzymatic activity, primarily via gingipains. The \u0394K\u0394RAB mutant biofilms caused less epithelial disruption and oxidative stress compared to the wild-type, highlighting the critical role of gingipains in pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Survival experiments using <jats:italic>Galleria mellonella<\/jats:italic> larvae supported these findings, highlighting the reduced survival associated with dual-species biofilms and the potential for high-dose antimicrobial therapies to mitigate this effect. These results emphasize the cooperative mechanisms of <jats:italic>C. albicans<\/jats:italic> and <jats:italic>P. gingivalis<\/jats:italic> in compromising epithelial barriers and underline the importance of combination therapies targeting both fungal and bacterial components in polymicrobial infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1552395","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T06:54:21Z","timestamp":1741330461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Synergistic effects of Candida albicans and Porphyromonas gingivalis biofilms on epithelial barrier function in a 3D aspiration pneumonia model"],"prefix":"10.3389","volume":"15","author":[{"given":"Ewelina","family":"Wronowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibeth","family":"Guevara-Lora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Brankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazyna","family":"Bras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Zawrotniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Satala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Karkowska-Kuleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Budziaszek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Koziel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rapala-Kozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00915-18","article-title":"Candida albicans-induced epithelial damage mediates translocation through intestinal barriers","volume":"9","author":"Allert","year":"2018","journal-title":"mBio"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106485","article-title":"Aspiration pneumonia: A renewed perspective and practical approach","volume":"185","author":"Almirall","year":"2021","journal-title":"Respir. 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