Abstract
Streptococcus mutans is the primary etiological agent associated with cariogenic process. The present study aimed to investigate the antibacterial and anti-virulence activities of theaflavins (TFs) to Streptococcus mutans UA159 as well as the underlying mechanisms. The results showed that TFs were capable of suppressing the acid production, cell adherence, water-insoluble exopolysaccharides production, and biofilm formation by S. mutans UA159 with a dosage-dependent manner while without influencing the cell growth. By a genome-wide transcriptome analysis (RNA-seq), we found that TFs attenuated the biofilm formation of S. mutans UA159 by inhibiting glucosyltransferases activity and the production of glucan-binding proteins (GbpB and GbpC) instead of directly blocking the expression of genes coding for glucosyltransferases. Further, TFs inhibited the expression of genes implicated in peptidoglycan synthesis, glycolysis, lipid synthesis, two-component system, signaling peptide transport (comA), oxidative stress response, and DNA replication and repair, suggesting that TFs suppressed the virulence factors of S. mutans UA159 by affecting the signal transduction and cell envelope stability, and weakening the ability of cells on oxidative stress resistance. In addition, an upregulated expression of the genes involved in protein biosynthesis, amino acid metabolism, and transport system upon TFs treatment indicated that cells increase the protein synthesis and nutrients uptake as one self-protective mechanism to cope with stress caused by TFs. The results of this study increase our current understanding of the anti-virulence activity of TFs on S. mutans and provide clues for the use of TFs in the prevention of dental caries.
Highlights
The human oral cavity is an ideal niche for the inhabitation of diverse microorganisms that constitute a predominant part of the human microbial library (Lamont et al 2018)
TFs exert antibacterial and anti‐virulence activities with a dosage‐dependent manner The growing concerns of the side effects produced by the use of traditional antibacterial agents such as chlorhexidine and fluoride for the prevention of dental caries caused by S. mutans has shifted the public attention to natural products (Singla et al 2018; Souissi et al 2021; Vijayakumar et al 2021)
Wang and co-workers showed that TF3 suppresses the biofilm formation, acid production, and acid tolerance by S. mutans UA159 (Wang et al 2019)
Summary
The human oral cavity is an ideal niche for the inhabitation of diverse microorganisms that constitute a predominant part of the human microbial library (Lamont et al 2018). The oral microbiota live in symbiosis with the host, contributing substantially to the healthy state by suppressing the proliferation of pathogenic microorganisms (Shang et al 2020). The imbalance of oral microbiota caused by factors like antibiotic treatment, sugar consumption, and overexposure to fermentable carbohydrate will lead to the development of oral diseases, such as dental caries and periodontitis, which gives rise to healthy risks (Bowen et al 2018; Lamont et al 2018). Kong et al AMB Expr (2021) 11:102 characterized by a decalcification of dental hard tissues is mainly caused by the accumulation of acidogenic and aciduric microorganisms, among which Streptococcus mutans is the primary etiological agent as it possesses diverse virulence features (Rather et al 2020). Inhibiting the biofilm formation of S. mutans is one important way for preventing dental caries development
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