{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:47:37Z","timestamp":1789584457988,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32402248"],"award-info":[{"award-number":["32402248"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin","doi-asserted-by":"crossref","award":["24JCQNJC00880"],"award-info":[{"award-number":["24JCQNJC00880"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Dental caries, a prevalent biofilm-mediated chronic disease, causes enamel demineralization, pulp infection, and systemic complications. Dental plaque biofilm is the initiating factor for the occurrence and development of caries. Streptococcus mutans is an opportunistic pathogen linked to the structure and ecology of dental plaque biofilms. The molecular mechanism of S. mutans during biofilm ontogeny in driving cariogenesis has been extensively elucidated. Here, we observed that asiatic acid is a potent biofilm disruptor that selectively dismantles S. mutans biofilm architectures, prompting us to investigate its mechanism. The minimum biofilm inhibition concentration (MBIC) of asiatic acid on S. mutans was 62.5 \u03bcM, but the MBIC level did not substantially impede planktonic growth. Using the static active-attachment model, it was demonstrated that asiatic acid significantly reduced biofilm biomass (p &lt; 0.001) and extracellular polysaccharides (EPS) content (p &lt; 0.001), while concurrently diminishing acid production (p = 0.017) and metabolic activity (p = 0.014). Confocal and scanning electron microscopy further confirmed structural disintegration, including bacterial detachment and reduced biofilm thickness. Transcriptome analysis of S. mutans biofilm treated with asiatic acid revealed 454 differentially expressed genes (adjusted p &lt; 0.05, |log2FC| \u2265 1). Notably, genes related to the CiaRH two-component system (ciaR, ciaH), a central regulatory hub for biofilm maturation and acid tolerance. This disruption initiates a downstream cascade, causing a coordinated downregulation of critical gene clusters essential for virulence and pathogenesis, including stress response (htrA, clpP, groEL, dnaK), and the glucan-binding protein gene (gbpC) essential for biofilm structural integrity. These findings provide the first mechanistic evidence linking asiatic acid to transcriptional reprogramming in S. mutans biofilm, offering a novel ecological strategy for caries prevention by targeting key regulatory pathways.<\/jats:p>","DOI":"10.3390\/ijms26199510","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asiatic Acid Disrupts the Biofilm Virulence of Streptococcus mutans by Transcriptional Reprogramming of Quorum Sensing System"],"prefix":"10.3390","volume":"26","author":[{"given":"Qingying","family":"Shi","sequence":"first","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhu","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"},{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, No. 235 Nanjing East Road, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Customs Animal, Plant, and Food Testing Center, No. 51, Second Avenue, Tianjin Economic-Technological Development Area (TEDA), Binhai New Area, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-8827","authenticated-orcid":false,"given":"Fuping","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1007\/s00784-019-03146-x","article-title":"Genes in the Pathway of Tooth Mineral Tissues and Dental Caries Risk: A Systematic Review and Meta-Analysis","volume":"24","author":"Chisini","year":"2020","journal-title":"Clin. 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