Targeted Gene Expression Analysis of Streptococcus mutans interaction with Oral Epithelial Cells in a Co-Culture Model

Streptococcus mutans is recognized as the principal etiological agent of dental caries and has also been implicated in systemic diseases such as bacterial endocarditis and inflammatory bowel disorders. Its pathogenicity is strongly associated with virulence traits, including quorum sensing, biofilm formation, and oxidative stress response. This study examined the transcriptional profile of selected S. mutans virulence-associated genes under different nutrient conditions, and growth states, and assessed corresponding host epithelial response using an in vitro co-culture model. Gene expression was examined during planktonic growth and biofilm formation in Brain Heart Infusion broth and chemically defined artificial saliva. In parallel, human TR146 buccal epithelial cells were co-cultured with S. mutans to evaluate the transcriptional response of host defense related genes. Results demonstrated that virulence-related genes involved in quorum sensing, polysaccharide synthesis and regulatory pathways exhibited higher expression during biofilm growth compared to planktonic cultures, with expression patterns influenced by nutrient composition. On the host side, several inflammatory mediators, including IL-1beta and IL-6 were consistently upregulated, highlighting their roles in bacterial challenge, whereas other genes, such as IL-8, showed an unexpected downregulation at several time points, suggesting possible immune evasion mechanisms. Together, these findings demonstrate coordinated transcriptional changes in both bacterial and host cells during co-cultures. The TR146- S. mutans model provides a valuable platform for studying the transcriptional responses associated with oral growth under defined in vitro conditions.