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Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study elucidated the critical role of the <jats:italic>liaS<\/jats:italic> gene in the <jats:italic>Streptococcus mutans<\/jats:italic> (<jats:italic>S. mutans<\/jats:italic>) two-component signal (TCS) transduction system during cross-kingdom interactions with <jats:italic>Candida albicans<\/jats:italic> (<jats:italic>C. albicans<\/jats:italic>). This gene governs the cariogenic potential of dual-species biofilms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression analysis of cocultured samples was performed. The survival rate during H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment in single and dual-species was assessed. Bacterial adhesion, extracellular polysaccharide (EPS) synthesis, acidic metabolite accumulation, and early adhesion of <jats:italic>C. albicans<\/jats:italic> in dual-species biofilms were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the wild-type (<jats:italic>WT<\/jats:italic>) and complemented strains (liaS<jats:sup>\u2013<\/jats:sup>-comp), liaS- exhibited impaired acid tolerance due to downregulated comDE expression. The <jats:italic>liaS<\/jats:italic> knockout mutant strain also presented reduced <jats:italic>vicRK<\/jats:italic> expression, leading to diminished glucosyltransferase (Gtf)-mediated bacterial adhesion, EPS synthesis, and acidic metabolite accumulation. Although <jats:italic>C. albicans<\/jats:italic> alleviated oxidative stress by secreting superoxide dismutase, liaS- markedly compromised the intracellular reactive oxygen species (ROS) scavenging capacity and reduced the survival rate during H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment in single and dual-species. Furthermore, liaS- inactivation suppressed the early adhesion of <jats:italic>C. albicans<\/jats:italic> in dual-species biofilms by reducing the synthesis of cyclic adenosine monophosphate (cAMP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work provides the first evidence that <jats:italic>liaS<\/jats:italic> orchestrates a multidimensional phenotypic regulatory network that coordinately modulates biofilm architecture and metabolic activity. This activity ultimately attenuates cariogenicity <jats:italic>in vivo<\/jats:italic>, thus highlighting liaS as a pivotal virulence determinant in cross-kingdom infections and emphasizing its potential as a therapeutic target against dental caries.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1612841","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T15:36:39Z","timestamp":1753976199000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["LiaS gene from two-component system is essential for caries pathogenicity in dual-species biofilms of Streptococcus mutans and Candida albicans"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanfan","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowu","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0042-2018","article-title":"Biology of oral streptococci.","volume":"6","author":"Abranches","year":"2018","journal-title":"Microbiol. 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