title: 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.
authors.affiliation: Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
authors.forename: Phuong Thi Mai
authors.initials: PT
authors.lastname: Nguyen
authors.affiliation: Center for Oral Biology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Falsetta
authors.affiliation: Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Geelsu
authors.initials: G
authors.lastname: Hwang
authors.affiliation: Center for Oral Biology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Mireya
authors.initials: M
authors.lastname: Gonzalez-Begne
authors.affiliation: Center for Oral Biology, University of Rochester Medical Center, Rochester, New York, United States of America; Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hyun
authors.initials: H
authors.lastname: Koo
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects*; D018533:Biomass; D017886:Durapatite / Q000737:chemistry; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D010770:Phosphotransferases / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry; D012463:Saliva / Q000737:chemistry / Q000382:microbiology; D013295:Streptococcus mutans / Q000187:drug effects*; D013314:Stress, Mechanical; D014744:Vietnam; D014774:Virulence; D044004:Xanthones / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D011134:Polysaccharides; D044004:Xanthones; D017886:Durapatite; C009689:xanthone; D010770:Phosphotransferases; D000251:Adenosine Triphosphatases; C021053:mangostin