Dental caries is a progressive disease of the tooth’s hard tissues. Untreated permanent dental caries remains the most common disease, with prevalence increasing by 53 % from 1990 to 2021 (GBD 2021 Oral Disorders Collaborators, 2025), resulting in significant health, social, and economic burdens. Excessive sugar intake and poor oral hygiene can disrupt oral microbial communities, leading to the formation of pathogenic biofilms (Baker et al., 2024). Dental plaque is a biofilm composed of bacteria and the extracellular matrix, with exopolysaccharides (EPS) as primary structural components. EPS enhance biofilm stability and protect microorganisms under fluctuating environmental conditions (Flemming et al., 2023, Gheorghita et al., 2023). Streptococcus mutans (S. mutans) is vital in biofilm formation due to its exceptional EPS synthesis ability (Lin et al., 2021, Zhang et al., 2022). Streptococcus sanguinis (S. sanguinis ) is a pioneer commensal species in dental biofilms, abundant in various oral sites (Kreth et al., 2017). Glucosyltransferases (Gtf) of S. mutans, encoded by the gtfB/C/D genes, convert sucrose into water-insoluble glucan and water-soluble glucan: the former contributes to biofilm structure, whereas the latter provides energy (Koo et al., 2013). DexA degrades water-soluble glucans, thereby regulating EPS balance (Yan et al., 2023). The VicRK two-component system plays a critical role in EPS synthesis by upregulating gtfB/C/D, ultimately promoting biofilm formation (Dmitriev et al., 2011, Lei et al., 2019, Senadheera et al., 2005).

Preventive strategies for dental caries often rely on mechanical plaque removal and fluoride application (Chan et al., 2022). However, chemical agents like chlorhexidine have adverse effects such as tooth staining and xerostomia. Antibiotics face limitations in biofilm penetration (Demessant-Flavigny et al., 2023, Poppolo Deus and Ouanounou, 2022). This has led to increased interest in Traditional Chinese Medicine (TCM) for oral health. Pudilan is a TCM preparation that consists of Scutellaria baicalensis, Taraxacum mongolicum, Corydalis bungeana, and Isatis indigotica. It has anti-inflammatory, multi-target antibacterial, and antioxidant activities (Tian et al., 2021). Pudilan has been used in oral treatments, such as reducing gingival inflammation and promoting ulcer healing (Cheng et al., 2019, Jin et al., 2017). Our prior research revealed that Pudilan reduced the viability of the S. mutans wild-type strain in biofilms. Additionally, the smc gene was downregulated in 8-hour biofilms but upregulated in 24-hour biofilms when treated with Pudilan (Ren et al., 2023), suggesting a potential regulatory role. However, most existing Pudilan studies have focused on chemical composition or clinical efficacy, with little attention to bacterial genetic responses or molecular mechanisms (Liu et al., 2021). Therefore, exploring the interaction between Pudilan and the smc gene offers a new perspective on empirical observations and mechanistic understanding.

Structural maintenance of chromosomes (SMC) complexes are conserved and essential for organizing chromosomes, including the regulation of DNA recombination and ensuring proper chromosome segregation (Hoencamp & Rowland, 2023). They also have a role in modulating cellular tolerance to environmental stresses: Deletion of the smc gene causes prolonged growth retardation in Streptococcus pneumoniae, as well as increased susceptibility to gyrase inhibitor drugs in Staphylococcus aureus (Kjos and Veening, 2014, Yu et al., 2010). In Bacillus subtilis, loss of smc results in hypersensitivity to antibiotics and lethality under conditions that promote rapid growth (Benoist et al., 2015, Gruber et al., 2014). These findings suggest that smc is also important for maintaining cellular fitness under environmental stress. S. mutans is frequently exposed to environmental fluctuations in the oral cavity, such as acid stress and oxidative stress. It is plausible that smc contributes to its stress adaptation. Pudilan may impose additional stress on S. mutans. Thus, this study investigates whether the smc gene modulates the inhibitory effects of Pudilan on S. mutans and its response to environmental stresses. In addition, we applied network pharmacology analysis and molecular docking to explore potential interactions between Pudilan components and key enzymes involved in EPS synthesis. These approaches aim to provide new insights into the genetic and pharmacological regulation of bacterial survival, exopolysaccharide synthesis, and biofilm formation.