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α-Mangostin (αMG) has been reported to be an effective antimicrobial agent against planktonic cells of  Streptococcus mutans , a biofilm-forming and acid-producing cariogenic organism. However, its anti-biofilm activity remains to be determined. We examined whether αMG, a xanthone purified from  Garcinia mangostana  L grown in Vietnam, disrupts the development, acidogenicity, and/or the mechanical stability of  S. mutans  biofilms. Treatment regimens simulating those experienced clinically (twice-daily, 60 s exposure each) were used to assess the bioactivity of αMG using a saliva-coated hydroxyapatite (sHA) biofilm model. Topical applications of early-formed biofilms with αMG (150 µM) effectively reduced further biomass accumulation and disrupted the 3D architecture of  S. mutans  biofilms. Biofilms treated with αMG had lower amounts of extracellular insoluble and intracellular iodophilic polysaccharides (30–45%) than those treated with vehicle control ( P <0.05), while the number of viable bacterial counts was unaffected. Furthermore, αMG treatments significantly compromised the mechanical stability of the biofilm, facilitating its removal from the sHA surface when subjected to a constant shear stress of 0.809 N/m 2  (>3-fold biofilm detachment from sHA vs. vehicle-treated biofilms;  P <0.05). Moreover, acid production by  S. mutans  biofilms was disrupted following αMG treatments (vs. vehicle-control,  P <0.05). The activity of enzymes associated with glucan synthesis, acid production, and acid tolerance (glucosyltransferases B and C, phosphotransferase-PTS system, and F 1 F 0 -ATPase) were significantly inhibited by αMG. The expression of  manL , encoding a key component of the mannose PTS, and  gtfB  were slightly repressed by αMG treatment ( P <0.05), while the expression of  atpD  (encoding F-ATPase) and  gtfC  genes was unaffected. Hence, this study reveals that brief exposures to αMG can disrupt the development and structural integrity of  S. mutans  biofilms, at least in part via inhibition of key enzymatic systems associated with exopolysaccharide synthesis and acidogenicity. αMG could be an effective anti-virulence additive for the control and/or removal of cariogenic biofilms.

α-Mangostin Disrupts the Development of Streptococcus mutans Biofilms and Facilitates Its Mechanical Removal