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

Abstract

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/m2 (>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 F1F0-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.

Probiotic Lactobacillus sp. inhibit growth, biofilm formation and gene expression of caries‐inducing Streptococcus mutans

“… Production of acid that damages dental hard tissues ; An agmatine deiminase system and F‐ATPase encoded by the aguBDAC operon and atpD gene , which are major components in acid‐adaptive response that contribute to the aciduric characteristics. The ability to synthesize exopolysaccharides (EPS) from sucrose by the action of multiple glucosyltransferases (Gtfs) encoded by the genes gtfb , gtfc , gtfd , in addition to fructosyltransferase encoded by sacB (ftf ) gene. The glucosyltransferase and fructosyltransferase enzymes catalyse the synthesis of extracellular glucan and fructan polymers from sucrose, respectively .…”

“…(ii) An agmatine deiminase system and F-ATPase encoded by the aguBDAC operon [9] and atpD gene [10], which are major components in acid-adaptive response that contribute to the aciduric characteristics. (iii) The ability to synthesize exopolysaccharides (EPS) from sucrose by the action of multiple glucosyltransferases (Gtfs) encoded by the genes gtfb, gtfc, gtfd, in addition to fructosyltransferase encoded by sacB (ftf) gene.…”

Anti-Biofilm Activity of a Self-Aggregating Peptide against Streptococcus mutans

“…Since early biofilm establishment by oral streptococci often precedes the attachment of other oral pathogens, inhibiting these biofilms may help prevent further disease (Xiao and Koo, 2010). Anti-biofilm molecules with activity against S. mutans and other oral streptococci include natural products such as alpha-mangostin (Thi et al, 2014), salivary mucin glycoprotein (Frenkel and Ribbeck, 2015), polysaccharide-degrading enzymes (Otsuka et al, 2015), MPC-polymers (Hirota et al, 2011), and small molecules that antagonize glucosyltransferases (Chen et al, 2015). …”

The inhibition of Streptococcus mutans glucosyltransferase enzyme activity by mangosteen pericarp extract

“…In the results of that research, amino acids in the chain of the Gtf enzyme were found to be strongly and stably bound with α mangostin, indicating the effects of α mangostin on the Gtf enzyme. 7 Based on the results of the analysis of those treatment groups using mangosteen pericarp extract, it could be seen that this extract at a concentration of 0.78% had greater inhibitory power against the activity of the Gtf enzyme (with a fructose level of 32.63%) than the mangosteen pericarp extract at a concentration of 0.39% (with a fructose level of 49.77%). Nevertheless, the results of the MannWhitney test showed there to be no significant difference between the two treatment groups.…”

“…However, the main one is GtfB because it can catalyze the formation of insoluble, alfa-linked glucan. 7 Inhibition of enzyme activity is also known to be caused by tannin which has an inhibitory power of 31.39%. 8 In addition, flavonoids also actively limit the activity of the Gtf enzyme as well as promoting antibacterial activity.…”