The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.
Alberti-SeguiCArndtACuginiCPriyadarshiniRDaveyME. 2010. HU protein affects transcription of surface polysaccharide synthesis genes in Porphyromonas gingivalis. J Bacteriol. 192(23):6217–6229.
2.
BainbridgeBWHiranoTGrieshaberNDaveyME. 2015. Deletion of a 77-base-pair inverted repeat element alters the synthesis of surface polysaccharides in Porphyromonas gingivalis. J Bacteriol. 197(7):1208–1220.
BerkVFongJCDempseyGTDeveliogluONZhuangXLiphardtJYildizFHChuS. 2012. Molecular architecture and assembly principles of Vibrio cholerae biofilms. Science. 337(6091):236–239.
5.
BowenWHBurneRAWuHKooH. 2018. Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenvironments. Trends Microbiol. 26(3):229–242.
6.
BowenWHKooH. 2011. Biology of Streptococcus mutans–derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 45(1):69–86.
7.
Castillo-PedrazaMCNovaisTFFaustoferriRCQuiveyRGJrTerekhovAHamakerBRKleinMI. 2017. Extracellular DNA and lipoteichoic acids interact with exopolysaccharides in the extracellular matrix of Streptococcus mutans biofilms. Biofouling. 33(9):722–740.
DasTSharmaPKBusscherHJvan der MeiHCKromBP. 2010. Role of extracellular DNA in initial bacterial adhesion and surface aggregation. Appl Environ Microbiol. 76(10):3405–3408.
10.
DaveyMEDuncanMJ. 2006. Enhanced biofilm formation and loss of capsule synthesis: deletion of a putative glycosyltransferase in Porphyromonas gingivalis. J Bacteriol. 188(15):5510–5523.
11.
DevarajAJusticeSSBakaletzLOGoodmanSD. 2015. DNABII proteins play a central role in UPEC biofilm structure. Mol Microbiol. 96(6):1119–1135.
12.
DewhirstFEChenTIzardJPasterBJTannerACYuWHLakshmananAWadeWG. 2010. The human oral microbiome. J Bacteriol. 192(19):5002–5017.
13.
DingYZhouYYaoJSzymanskiCFredricksonJShiLCaoBZhuZYuXY. 2016. In situ molecular imaging of the biofilm and its matrix. Anal Chem. 88(22):11244–11252.
FontanaCLiSYangZWidmalmG. 2015. Structural studies of the exopolysaccharide from Lactobacillus plantarum C88 using NMR spectroscopy and the program CASPER. Carbohydr Res. 402:87–94.
16.
GoodmanSDObergfellKPJurcisekJANovotnyLADowneyJSAyalaEATjokroNLiBJusticeSSBakaletzLO. 2011. Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins. Mucosal Immunol. 4(6):625–637.
17.
HeJHwangGLiuYGaoLKilpatrick-LivermanLSantarpiaPZhouXKooH. 2016. L-arginine modifies the exopolysaccharide matrix and thwarts Streptococcus mutans outgrowth within mixed-species oral biofilms. J Bacteriol. 198(19):2651–2661.
18.
HobleyLHarkinsCMacPheeCEStanley-WallNR. 2015. Giving structure to the biofilm matrix: an overview of individual strategies and emerging common themes. FEMS Microbiol Rev. 39(5):649–669.
19.
HuWLiLSharmaSWangJMcHardyILuxRYangZHeXGimzewskiJKLiYet al. 2012. DNA builds and strengthens the extracellular matrix in Myxococcus xanthus biofilms by interacting with exopolysaccharides. PLoS One. 7(12):e51905.
20.
HuangXZhangKDengMExterkateRAMLiuCZhouXChengLTen CateJM. 2017. Effect of arginine on the growth and biofilm formation of oral bacteria. Arch Oral Biol. 82:256–262.
21.
HwangGLiuYKimDSunVAviles-ReyesAKajfaszJKLemosJAKooH. 2016. Simultaneous spatiotemporal mapping of in situ pH and bacterial activity within an intact 3D microcolony structure. Sci Rep. 6:32841.
22.
ItoKItoSShimamuraTWeyandSKawarasakiYMisakaTAbeKKobayashiTCameronADIwataS. 2011. Crystal structure of glucansucrase from the dental caries pathogen Streptococcus mutans. J Mol Biol. 408(2):177–186.
23.
IzanoEASadovskayaIWangHVinogradovERagunathCRamasubbuNJabbouriSPerryMBKaplanJB. 2008. Poly-N-acetylglucosamine mediates biofilm formation and detergent resistance in Aggregatibacter actinomycetemcomitans. Microb Pathog. 44(1):52–60.
24.
KleinMIHwangGSantosPHCampanellaOHKooH. 2015. Streptococcus mutans–derived extracellular matrix in cariogenic oral biofilms. Front Cell Infect Microbiol. 5:10.
25.
KooHFalsettaMLKleinMI. 2013. The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm. J Dent Res. 92(12):1065–1073.
26.
KuramitsuHK. 2003. Molecular genetic analysis of the virulence of oral bacterial pathogens: an historical perspective. Crit Rev Oral Biol Med. 14(5):331–344.
27.
KuramitsuHKWondrackLMcGuinnessM. 1980. Interaction of Streptococcus mutans glucosyltransferases with teichoic acids. Infect Immun. 29(2):376–382.
28.
LiaoSKleinMIHeimKPFanYBitounJPAhnSJBurneRAKooHBradyLJWenZT. 2014. Streptococcus mutans extracellular DNA is upregulated during growth in biofilms, actively released via membrane vesicles, and influenced by components of the protein secretion machinery. J Bacteriol. 196(13):2355–2366.
29.
LiuJStoneVNGeXTangMElramiFXuP. 2017. TetR family regulator brpT modulates biofilm formation in Streptococcus sanguinis. PLoS One. 12(1):e0169301.
30.
Mashburn-WarrenLDowneyJSGoodmanSD. 2017. Novel method for the depletion of cariogenic bacteria using dextranomer microspheres. Mol Oral Microbiol. 32(6):475–489.
31.
MillerDPHutchersonJAWangYNowakowskaZMPotempaJYoder-HimesDRScottDAWhiteleyMLamontRJ. 2017. Genes contributing to Porphyromonas gingivalis fitness in abscess and epithelial cell colonization environments. Front Cell Infect Microbiol. 7:378.
32.
MunozVLPorschEASt GemeJW3rd. 2018. Kingella kingae surface polysaccharides promote resistance to human serum and virulence in a juvenile rat model. Infect Immun. 86(6). pii: e00100-18.
33.
NadellCDDrescherKFosterKR. 2016. Spatial structure, cooperation and competition in biofilms. Nat Rev Microbiol. 14(9):589–600.
34.
NascimentoMMBrowngardtCXiaohuiXKlepac-CerajVPasterBJBurneRA. 2014. The effect of arginine on oral biofilm communities. Mol Oral Microbiol. 29(1):45–54.
35.
NijampatnamBZhangHCaiXMichalekSMWuHVeluSE. 2018. Inhibition of Streptococcus mutans biofilms by the natural stilbene piceatannol through the inhibition of glucosyltransferases. ACS Omega. 3(7):8378–8385.
36.
NurAHirotaKYumotoHHiraoKLiuDTakahashiKMurakamiKMatsuoTShuRMiyakeY. 2013. Effects of extracellular DNA and DNA-binding protein on the development of a Streptococcus intermedius biofilm. J Appl Microbiol. 115(1):260–270.
PetersonBWvan der MeiHCSjollemaJBusscherHJSharmaPK. 2013. A distinguishable role of eDNA in the viscoelastic relaxation of biofilms. MBio. 4(5):e00497-00413.
39.
RoccoCJBakaletzLOGoodmanSD. 2018. Targeting the HUbeta protein prevents Porphyromonas gingivalis from entering into preexisting biofilms. J Bacteriol. 200(11). pii: e00790-17.
40.
RoccoCJDaveyMEBakaletzLOGoodmanSD. 2017. Natural antigenic differences in the functionally equivalent extracellular DNABII proteins of bacterial biofilms provide a means for targeted biofilm therapeutics. Mol Oral Microbiol. 32(2):118–130.
41.
SawenEHuttunenEZhangXYangZWidmalmG. 2010. Structural analysis of the exopolysaccharide produced by Streptococcus thermophilus ST1 solely by NMR spectroscopy. J Biomol NMR. 47(2):125–134.
42.
ShanmugamMEl AbbarFRamasubbuN. 2015. Transcriptome profiling of wild-type and pga-knockout mutant strains reveal the role of exopolysaccharide in Aggregatibacter actinomycetemcomitans. PLoS One. 10(7):e0134285.
43.
SinghAWyantTAnaya-BergmanCAduse-OpokuJBrunnerJLaineMLCurtisMALewisJP. 2011. The capsule of Porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence. Infect Immun. 79(11):4533–4542.
44.
Skov-SorensenUBYaoKYangYTettelinHKilianM. 2016. Capsular polysaccharide expression in commensal Streptococcus species: genetic and antigenic similarities to Streptococcus pneumoniae. MBio. 7(6). pii: e01844-16.
45.
StewartPSFranklinMJ. 2008. Physiological heterogeneity in biofilms. Nat Rev Microbiol. 6(3):199–210.
46.
TangWBhattASmithANCrowleyPJBradyLJLongJR. 2016. Specific binding of a naturally occurring amyloidogenic fragment of Streptococcus mutans adhesin P1 to intact P1 on the cell surface characterized by solid state NMR spectroscopy. J Biomol NMR. 64(2):153–164.
47.
VenketaramanVLinAKLeAKachlanySCConnellNDKaplanJB. 2008. Both leukotoxin and poly-N-acetylglucosamine surface polysaccharide protect Aggregatibacter actinomycetemcomitans cells from macrophage killing. Microb Pathog. 45(3):173–180.
WangXDubeyAKSuzukiKBakerCSBabitzkePRomeoT. 2005. CsrA post-transcriptionally represses pgaABCD, responsible for synthesis of a biofilm polysaccharide adhesin of Escherichia coli. Mol Microbiol. 56(6):1648–1663.
50.
WangXSharpCEJonesGMGrasbySEBradyALDunfieldPF. 2015. Stable-isotope probing identifies uncultured Planctomycetes as primary degraders of a complex heteropolysaccharide in soil. Appl Environ Microbiol. 81(14):4607–4615.
51.
WashioJTakahashiN. 2016. Metabolomic studies of oral biofilm, oral cancer, and beyond. Int J Mol Sci. 17(6). pii: E870.
52.
WebbJSThompsonLSJamesSCharltonTTolker-NielsenTKochBGivskovMKjellebergS. 2003. Cell death in Pseudomonas aeruginosa biofilm development. J Bacteriol. 185(15):4585–4592.
53.
XiaoJKleinMIFalsettaMLLuBDelahuntyCMYatesJRIIIHeydornAKooH. 2012. The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm. PLoS Pathog. 8(4):e1002623.
54.
YagupskyPPorschESt GemeJW3rd. 2011. Kingella kingae: an emerging pathogen in young children. Pediatrics. 127(3):557–565.
55.
YamamotoRNoiriYYamaguchiMAsahiYMaezonoHKuboniwaMHayashiMEbisuS. 2013. The sinR ortholog PGN_0088 encodes a transcriptional regulator that inhibits polysaccharide synthesis in Porphyromonas gingivalis ATCC 33277 biofilms. PLoS One. 8(2):e56017.
56.
YamanakaTYamaneKFurukawaTMatsumoto-MashimoCSugimoriCNambuTObataNWalkerCBLeungKPFukushimaH. 2011. Comparison of the virulence of exopolysaccharide-producing Prevotella intermedia to exopolysaccharide non-producing periodontopathic organisms. BMC Infect Dis. 11:228.
57.
YoshidaYKonnoHNaganoKAbikoYNakamuraYTanakaYYoshimuraF. 2014. The influence of a glucosyltransferase, encoded by gtfP, on biofilm formation by Streptococcus sanguinis in a dual-species model. APMIS. 122(10):951–960.
58.
ZhangWSeminaraASuarisMBrennerMPDavidAWeitzDAAngeliniTA. 2014. Nutrient depletion in Bacillus subtilis biofilms triggers matrix production. New J Physi. 16. doi:10.1088/1367-2630/16/1/015028
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