Baicalein Inhibits Streptococcus mutans Biofilms and Dental Caries-Related Virulence Phenotypes

Abstract

Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need to identify compounds that curb the virulence of pathobionts without microbial killing. Through this study, we have demonstrated for the first time that 5,6,7-trihydroxyflavone (Baicalein) significantly downregulates crucial caries-related virulence phenotypes in Streptococcus mutans. Baicalein significantly inhibited biofilm formation by Streptococcus mutans UA159 (MBIC50 = 200 μM), without significant growth inhibition. Notably, these concentrations of baicalein did not affect the commensal S. gordonii. Strikingly, baicalein significantly reduced cell surface hydrophobicity, autoaggregation and acid production by S. mutans. Mechanistic studies (qRT-PCR) showed downregulation of various genes regulating biofilm formation, surface attachment, quorum sensing, acid production and competence. Finally, we demonstrate the potential translational value of baicalein by reporting synergistic interaction with fluoride against S. mutans biofilms.

Out of control: The need for standardised solvent approaches and data reporting in antibiofilm assays incorporating dimethyl-sulfoxide (DMSO)

“…2 ; Supplementary spreadsheet). Other methods included visualising biofilms grown on glass slides or coverslips by confocal or scanning electron microscopy [ 37 , 38 ], quorum sensing assays [ [39] , [40] , [41] ], and novel experimental approaches such as scraping or sonicating biofilms off growth surfaces and culturing on agar to determine viable colonies [ 37 , [42] , [43] , [44] , [45] ].

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Mechanistic insights into the inhibitory effect of theaflavins on virulence factors production in Streptococcus mutans

“…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 ). As an example, baicalein, a flavonoid isolated from the roots of Scutellaria baicalensis and Scutellaria lateriflora , is capable of inhibiting the biofilm formation, acid production, and cell surface hydrophobicity in S. mutans while without inhibiting its growth (Vijayakumar et al 2021 ). Theaflavins are the main bioactive component of black tea, which mainly contains four monomers including theaflavin (TF1), theaflavin-3-gallate (TF2a), theaflavin-3′-gallate (TF2b), and theaflavin-3, 3′-digallate (TF3) (Zhang et al 2020a , b ).…”

“…Dental caries 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 ). S. mutans is capable of metabolizing the dietary carbohydrates to produce diverse organic acids that induce the demineralization of enamel, resulting in the progression of dental caries (Vijayakumar et al 2021 ). Furthermore, the robust ability to form biofilm and adapt to stressful conditions during host colonization enables S. mutans to adhere enduringly to the tooth surface and escape from elimination by general oral cleaning and care (Souissi et al 2021 ; Priya et al 2021 ).…”

Strategies to Combat Caries by Maintaining the Integrity of Biofilm and Homeostasis during the Rapid Phase of Supragingival Plaque Formation

“…Other flavonoids with a high capacity to interfere with the uptake of glucose and other metabolites in S. mutans and other cariogenic bacteria are the phytoalexin flavones and the erycristagallin present in Erythrina variegata (Leguminosae) [ 68 ]. The therapeutic effect of baicalein (5,6,7-trihydroxyflavone), a flavonoid present in Scutellaria baicalensis and Scutellaria lateriflora , is being evaluated but is believed to affect the expression of several virulence genes that interact with the genes of S. mutans , which would alter the progression of biofilm to caries [ 74 ]. Propolis contains flavonoids which have conferred good antimicrobial activity against a number of oral bacteria and inhibition of the adherence of S. mutans and Streptococcus sobrinus [ 68 ].…”