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.
Highlights
Many infectious diseases in human are caused by virulent biofilms, including oral diseases [1]
Streptococcus mutans has been recognized as one of the key etiologic agents associated with the initiation of dental caries, additional organisms may contribute to its pathogenesis [9]
S. mutans biofilms were initially treated with a-mangostin at concentrations of 100, 150, and 200 mM (Table S1) based on bioactivity against planktonic S. mutans cells [27] and solubility in the vehicle system
Summary
Many infectious diseases in human are caused by virulent biofilms, including oral diseases [1]. For organisms associated with caries development, the production of an extracellular polysaccharide (EPS)-rich biofilm matrix, acidification of the milieu, and the maintenance of acidic pH microenvironment in close proximity to the tooth enamel are major controlling virulence factors linked with the pathogenesis of the disease. Current therapeutic approaches to control pathogenic oral biofilms fall short; the search for new/improved agents may lead to more efficacious anti-caries therapies [4,5,6]. Natural products are currently regarded as potentially promising sources for new bioactive agents that may function to suppress these key virulence attributes that are associated with the establishment and maintenance of cariogenic biofilms [5]. Streptococcus mutans has been recognized as one of the key etiologic agents associated with the initiation of dental caries, additional organisms may contribute to its pathogenesis [9]. S. mutans produces acid and is highly aciduric, allowing it to tolerate and continue to produce acids in low pH
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