Bacterial glycosyltransferases play important roles in bacterial fitness and virulence. Oral streptococci have evolved diverse strategies to survive and thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2 important biological processes mediated by 2 distinct groups of glycosyltransferases in oral streptococci that are important for bacterial colonization and virulence. The first process is the glycosylation of highly conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using Streptococcus parasanguinis as a model, we highlight new features of several glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1. Distinct features of a novel glycosyltransferase fold from a domain of unknown function 1792 are contrasted with common properties of canonical glycosyltransferases. The second biological process we cover is involved in building sticky glucan matrix to establish cariogenic biofilms by an important opportunistic pathogen Streptococcus mutans through the action of a family of 3 glucosyltransferases. We focus on discussing the structural feature of this family as a glycoside hydrolase family of enzymes. While the 2 processes are distinct, they all produce carbohydrate-coated biomolecules, which enable bacteria to stick better in the complex oral microbiome. Understanding the making of the sweet modification presents a unique opportunity to develop novel antiadhesion and antibiofilm strategies to fight infections by oral streptococci and beyond.
BiswasSBiswasI. 2006. Regulation of the glucosyltransferase (gtfBC) operon by CovR in Streptococcus mutans. J Bacteriol. 188(3):988–998.
2.
BowenWHKooH. 2011. Biology of Streptococcus mutans–derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 45(1):69–86.
3.
BuSLiYZhouMAzadinPZengMFives-TaylorPWuH. 2008. Interaction between two putative glycosyltransferases is required for glycosylation of a serine-rich streptococcal adhesin. J Bacteriol. 190(4):1256–1266.
4.
BuchanRAJenkinsonHF. 1990. Glucosyltransferase production by Streptococcus sanguis Challis and comparison with other oral streptococci. Oral Microbiol Immunol. 5(2):63–71.
5.
BuschCHofmannFSelzerJMunroSJeckelDAktoriesK. 1998. A common motif of eukaryotic glycosyltransferases is essential for the enzyme activity of large clostridial cytotoxins. J Biol Chem. 273(31):19566–19572.
6.
CampbellJADaviesGJBuloneVHenrissatB. 1997. A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem J. 326(Pt 3):929.
7.
CharnockSJDaviesGJ. 1999. Structure of the nucleotide-diphospho-sugar transferase, SpsA from Bacillus subtilis, in native and nucleotide-complexed forms. Biochemistry. 38(20):6380–6385.
8.
ChazeTGuillotAValotBLangellaOChamot-RookeJDi GuilmiAMTrieu-CuotPDramsiSMistouMY. 2014. O-glycosylation of the N-terminal region of the serine-rich adhesin Srr1 of Streptococcus agalactiae explored by mass spectrometry. Mol Cell Proteomics. 13(9):2168–2182.
9.
ClarkeAJHurtado-GuerreroRPathakSSchüttelkopfAWBorodkinVShepherdSMIbrahimAFvan AaltenDM. 2008. Structural insights into mechanism and specificity of O-GlcNAc transferase. Embo J. 27(20):2780–2788.
CoutinhoPMDeleuryEDaviesGJHenrissatB. 2003. An evolving hierarchical family classification for glycosyltransferases. J Mol Biol. 328(2):307–317.
12.
FalsettaMLKleinMIColonnePMScott-AnneKGregoireSPaiCHGonzalez-BegneMWatsonGKrysanDJBowenWH. 2014. Symbiotic relationship between Streptococcus mutans and Candida albicans synergizes virulence of plaque biofilms in vivo. Infect Immun. 82(5):1968–1981.
13.
GregoireSXiaoJSilvaBBGonzalezIAgidiPSKleinMIAmbatipudiKSRosalenPLBausermanRWaughRE. 2011. Role of glucosyltransferase B in interactions of Candida albicans with Streptococcus mutans and with an experimental pellicle on hydroxyapatite surfaces. Appl Environ Microbiol. 77(18):6357–6367.
14.
HamadaSSladeHD. 1980. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 44(2):331–384.
15.
HassinenAPujolFMKokkonenNPietersCKihlströmMKorhonenKKellokumpuS. 2011. Functional organization of Golgi N- and O-glycosylation pathways involves pH-dependent complex formation that is impaired in cancer cells. J Biol Chem. 286(44):38329–38340.
16.
HeckelTCzupallaCExpirto SantoAIAniteiMArantzazu Sanchez-FernandezMMoschKKrauseEHoflackB. 2009. Src-dependent repression of ARF6 is required to maintain podosome-rich sealing zones in bone-digesting osteoclasts. Proc Natl Acad Sci U S A. 106(5):1451–1456.
17.
HellmuthHWittrockSKraljSDijkhuizenLHoferBSeibelJ. 2008. Engineering the glucansucrase GTFR enzyme reaction and glycosidic bond specificity: toward tailor-made polymer and oligosaccharide products. Biochemistry. 47(25):6678–6684.
18.
IguraMMaitaNKamishikiryoJYamadaMObitaTMaenakaKKohdaD. 2008. Structure-guided identification of a new catalytic motif of oligosaccharyltransferase. EMBO J. 27(1):234–243.
19.
ItoKItoSShimamuraTWeyandSKawarasakiYMisakaTAbeKKobayashiTCameronADIwataS. 2011. Crystal structure of glucansucrase from the dental caries pathogen Streptococcus mutans. J Mol Biol. 408(2):177–186.
20.
JenkinsonHF. 2011. Beyond the oral microbiome. Environ Microbiol. 13(12):3077–3087.
21.
JeonJGRosalenPLFalsettaMLKooH. 2011. Natural products in caries research: current (limited) knowledge, challenges and future perspective. Caries Res. 45(3):243–263.
22.
KolenbranderPEGaneshkumarNCasselsFJHughesCV. 1993. Coaggregation-specific adherence among human oral plaque bacteria. FASEB J. 7(5):406–413.
23.
KolenbranderPEPalmerRJJrRickardAHJakubovicsNSChalmersNIDiazPI. 2006. Bacterial interactions and successions during plaque development. Periodontol2000. 42:47–79.
24.
KooHXiaoJKleinMIJeonJG. 2010. Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol. 192(12):3024–3032.
25.
KrzysciakWPluskwaKKJurczakAKoscielniakD. 2013. The pathogenicity of the Streptococcus genus. Eur J Clin Microbiol Infect Dis. 32(11):1361–1376.
26.
LairsonLLHenrissatBDaviesGJWithersSG. 2008. Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 77:521–555.
27.
LazarusMBNamYJiangJSlizPWalkerS. 2011. Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature. 469(7331):564–567.
28.
LemosJAQuiveyRGJrKooHAbranchesJ. 2013. Streptococcus mutans: a new Gram-positive paradigm?Microbiology. 159(Pt 3):436–445.
29.
LiYHuangXLiJZengJZhuFFanWHuL. 2014. Both GtfA and GtfB are required for SraP glycosylation in Staphylococcus aureus. Curr Microbiol. 69(2):121–126.
30.
LizcanoASanchezCJOrihuelaCJ. 2012. A role for glycosylated serine-rich repeat proteins in gram-positive bacterial pathogenesis. Mol Oral Microbiol. 27(4):257–269.
31.
LombardVGolaconda RamuluHDrulaECoutinhoPMHenrissatB. 2014. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 42(Database Issue):D490–D495.
32.
Martinez-FleitesCMacauleyMSHeYShenDLVocadloDJDaviesGJ. 2008. Structure of an O-GlcNAc transferase homolog provides insight into intracellular glycosylation. Nat Struct Mol Biol. 15(7):764–765.
33.
MonchoisVWillemotRMMonsanP. 1999. Glucansucrases: mechanism of action and structure-function relationships. FEMS Microbiol Rev. 23(2):131–151.
34.
NewbrunEHooverCIWalkerGJ. 1983. Inhibition by acarbose, nojirimycin and 1-deoxynojirimycin of glucosyltransferase produced by oral streptococci. Arch Oral Biol. 28(6):531–536.
35.
PedersenLCTsuchidaKKitagawaHSugaharaKDardenTANegishiM. 2000. Heparan/chondroitin sulfate biosynthesis structure and mechanism of human glucuronyltransferase I. J Biol Chem. 275(44):34580–34585.
36.
SeifertKNAddersonEEWhitingAABohnsackJFCrowleyPJBradyLJ. 2006. A unique serine-rich repeat protein (Srr-2) and novel surface antigen (epsilon) associated with a virulent lineage of serotype III Streptococcus agalactiae. Microbiology. 152(Pt 4):1029–1040.
37.
SenadheeraMDGuggenheimBSpataforaGAHuangYCChoiJHungDCTreglownJSGoodmanSDEllenRPCvitkovitchDG. 2005. A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J Bacteriol. 187(12):4064–4076.
38.
ShiWWJiangYLZhuFYangYHShaoQYYangHBRenYMWuHChenYZhouCZ. 2014. Structure of a novel O-linked N-acetyl-d-glucosamine (O-GlcNAc) transferase, GtfA, reveals insights into the glycosylation of pneumococcal serine-rich repeat adhesins. J Biol Chem. 289(30):20898–20907.
39.
ShimamuraANakanoYJMukasaHKuramitsuHK. 1994. Identification of amino acid residues in Streptococcus mutans glucosyltransferases influencing the structure of the glucan product. J Bacteriol. 176(16):4845–4850.
40.
StephensonAEWuHNovakJTomanaMMintzKFives-TaylorP. 2002. The Fap1 fimbrial adhesin is a glycoprotein: antibodies specific for the glycan moiety block the adhesion of Streptococcus parasanguis in an in vitro tooth model. Mol Microbiol. 43(1):147–157.
41.
SulavikMCClewellDB. 1996. Rgg is a positive transcriptional regulator of the Streptococcus gordonii gtfG gene. J Bacteriol. 178(19):5826–5830.
42.
TakamatsuDBensingBASullamPM. 2004. Genes in the accessory sec locus of Streptococcus gordonii have three functionally distinct effects on the expression of the platelet-binding protein GspB. Mol Microbiol52(1):189–203.
43.
ThurnheerTBelibasakisGNBostanciN. 2014. Colonisation of gingival epithelia by subgingival biofilms in vitro: role of “red complex” bacteria. Arch Oral Biol. 59(9):977–986.
44.
Van den SteenPRuddPMDwekRAOpdenakkerG. 1998. Concepts and principles of O-linked glycosylation. Crit Rev Biochem Mol Biol. 33(3):151–208.
45.
van HijumSAKraljSOzimekLKDijkhuizenLvan Geel-SchuttenIG. 2006. Structure-function relationships of glucansucrase and fructansucrase enzymes from lactic acid bacteria. Microbiol Mol Biol Rev. 70(1):157–176.
46.
VickermanMMClewellDB. 1997. Regulation of Streptococcus gordonii glucosyltransferase. Adv Exp Med Biol. 418:661–664.
47.
VickermanMMSulavikMCMinickPEClewellDB. 1996. Changes in the carboxyl-terminal repeat region affect extracellular activity and glucan products of Streptococcus gordonii glucosyltransferase. Infect Immun. 64(12):5117–5128.
48.
WuHBuSNewellPChenQFives-TaylorP. 2007a. Two gene determinants are differentially involved in the biogenesis of Fap1 precursors in Streptococcus parasanguis. J Bacteriol. 189(4):1390–1398.
49.
WuHMintzKPLadhaMFives-TaylorPM. 1998. Isolation and characterization of Fap1, a fimbriae-associated adhesin of Streptococcus parasanguis FW213. Mol Microbiol. 28(3):487–500.
50.
WuHZengMFives-TaylorP. 2007b. The glycan moieties and the N-terminal polypeptide backbone of a fimbria-associated adhesin, Fap1, play distinct roles in the biofilm development of Streptococcus parasanguinis. Infect Immun. 75(5):2181–2188.
51.
WuRWuH. 2011. A molecular chaperone mediates a two-protein enzyme complex and glycosylation of serine-rich streptococcal adhesins. J Biol Chem. 286(40):34923–34931.
52.
WuRZhouMWuH. 2010. Purification and characterization of an active N-acetylglucosaminyltransferase enzyme complex from Streptococci. Appl Environ Microbiol. 76(24):7966–7971.
53.
XuDQThompsonJCisarJO. 2003. Genetic loci for coaggregation receptor polysaccharide biosynthesis in Streptococcus gordonii 38. J Bacteriol. 185(18):5419–5430.
54.
ZhangHZhuFDingLZhouMWuRWuH. 2013. Preliminary X-ray crystallographic studies of an N-terminal domain of unknown function from a putative glycosyltransferase from Streptococcus parasanguinis. Acta Crystallogr Sect F Struct Biol Cryst Commun. 69(Pt 5):520–523.
55.
ZhangHZhuFYangTDingLZhouMLiJHaslamSMDellAErlandsenHWuH. 2014. The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. Nat Commun. 5:4339.
56.
ZhouMWuH. 2009. Glycosylation and biogenesis of a family of serine-rich bacterial adhesins. Microbiology. 155(Pt 2):317–327.
57.
ZhouMZhuFDongSPritchardDGWuH. 2010. A novel glucosyltransferase is required for glycosylation of a serine-rich adhesin and biofilm formation by Streptococcus parasanguinis. J Biol Chem. 285(16):12140–12148.
58.
ZhuFErlandsenHDingLLiJHuangYZhouMLiangXMaJWuH. 2011. Structural and functional analysis of a new subfamily of glycosyltransferases required for glycosylation of serine-rich streptococcal adhesins. J Biol Chem. 286(30):27048–27057.
59.
ZhuFZhangHWuH. 2014. A conserved domain is crucial for acceptor substrate binding in a family of glucosyltransferases. J Bacteriol. 197(3):510–517.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
