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Quorum-quenching enzymes, such as the AHL-lactonase Est816, offer a promising therapeutic strategy to disrupt microbial pathogenicity. This study investigated the anti-biofilm, anti-virulence, immunomodulatory, biocompatibility, and osteogenic properties of Est816 against <jats:italic>P. gingivalis<\/jats:italic>, exploring its therapeutic potential for peri-implantitis management.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>\n              <jats:italic>P. gingivalis<\/jats:italic> (ATCC 33277) was cultured on titanium discs and treated with Est816 (<jats:italic>P. gingivalis<\/jats:italic>\u2009+\u2009Est816). Biofilm morphology, biomass, viability, and kinetics were assessed using scanning electron microscopy (SEM), crystal violet staining, confocal laser scanning microscope (CLSM), and colony-forming unit (CFU) counting. Exopolysaccharide (EPS) production was quantified via phenol-sulfuric acid assay, while virulence gene expression was analyzed by RT-PCR. Cytotoxicity of Est816 on human oral keratinocytes (HOKs) was assessed using immunofluorescent microscopy. The immunodulatory impact of Est816 on <jats:italic>P. gingivalis<\/jats:italic> infected human periodontal ligament stem cells (PDLSCs) was assessed via ELISA and RT-PCR. Osteogenic differentiation of PDLSCs was examined by alizarin red staining.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Est816 treatment disrupted biofilm architecture (SEM), reducing biomass (crystal violet: 88% decrease, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), viability (CLSM: live\/dead ratio 0.3 vs. 5.7 control, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), and CFU counts (2.8-log reduction, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). EPS production decreased by 44% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and virulence gene expression was significantly suppressed (<jats:italic>rgpA<\/jats:italic>: 80%, <jats:italic>kgp<\/jats:italic>: 76%, <jats:italic>fimA<\/jats:italic>: 73%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Est816 exhibited no cytotoxicity toward HOKs and attenuated pro-inflammatory cytokine secretion in PDLSCs (TNF-\u03b1: 2.4-fold, IL-1\u03b2: 2.3-fold, IL-6: 11-fold, IL-8: 14-fold, reduction, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Furthermore, Est816 alone had no effect on the osteogenic differentiation of PDLSCs; however, it abolished the inhibitory effect of AHLs, significantly enhancing mineralized nodule formation by 1.4-fold (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) compared to the AHL-treated control.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Est816 exhibited anti-biofilm property, attenuated virulence release in <jats:italic>P. gingivalis<\/jats:italic>, and counteracted AHL-mediated suppression of osteoblast differentiation in PDLSCs, highlighting its dual therapeutic role in both pathogen inhibition and host tissue regeneration for peri-implantitis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12903-025-06563-5","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T16:10:50Z","timestamp":1752682250000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Quorum quenching by Est816: a novel approach to control Porphyromonas gingivalis pathogenicity"],"prefix":"10.1186","volume":"25","author":[{"given":"Zelda Ziyi","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Hung","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"6563_CR1","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1111\/odi.14782","volume":"30","author":"X Wei","year":"2024","unstructured":"Wei X, Qian S, Yang Y, Mo J. 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