Show legend Show as text

Structure type: oligomer
Aglycon: CH2CH2CH3
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_225177,IEDB_885823

• Article ID: 387
  Stuike-Prill R, Pinto BM "Conformational analysis of oligosaccharides corresponding to the cell-wall polysaccharide of the Streptococcus group A by Metropolis Monte Carlo simulations" - Carbohydrate Research 279 (1995) 59-73
  

  Metropolis Monte Carlo simulations have been performed on four substructures from the call-wall polysaccharide antigen of Streptococcus group A to explore the conformational begaviour of these compounds. The compounds examined are the trisaccharide, propyl 3-O-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-2-O-(a-L-rhamnopyranosyl)-a-L-rhamnopyranoside, 1, the tetrasaccharide, propyl 3-O-(3-O-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-2-O-(a-L-rhamnopyranosyl)-a-L-rhamnopyranosyl)-a-L-rhamnopyranoside, 2, the hexasacchride, propyl 3-O-(2-O-(3-O-(3-O-(2-acetamido-2-deoxy-bDglucopyranosyl)-a-L-rhamnopyranosyl)-a-L-rhamnopyranosyl)-3-O-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-a-L-rhamnopyranosyl)-a-L-rhamnopyranoside, 3, and the hexasaccharide, propyl 3-O-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-2-O-(3-O-(3-O-(2-acetamido-2-deoxy-b-D-glucopyranosyl)-2-O-(a-L-rhamnopyranosyl)-a-L-rhamnopyranosyl)-a-L-rhamnopyranosyl)-a-L-rhamnopyranoside, 4. In general, the conformational flexibility of simular glycosidic linkages in different compounds is comparable. However, in a few cases, small differences in the conformations available to these linkages in different structural environments could be detected. Interestingly, a secon conformation found for the b-D-GlcNAc-(1→3)-a-L-Rha linkage in three of the compounds was not populated in the hexasaccharide 4. Futhermore, a conformational locale of the a-L-Rha-(1→3)-a-L-Rha linkage found to by populated in the trisaccaharide 1, tetrasaccahride 2, and hexasaccharide 4 is negligibly populated in the hexasaccharide 3. Ensemble averaged proton-proton disances compare favourably with experimental average distances obtained fro mNMR spectroscopy. The trisaccharide branch point in the hexasaccharides is shown to by a hoghly defined conformational feature. The same unit has been found to by one of the crucial elements recognized by anti-Group A Streptococcus antibodies, a result that has implications for the design of improved immunodiagnostics and vaccines.

  Oligosaccharides, Metropolis Monte Carlo simulations, Cell-wall polysaccharide, Streptococcus group A

  NCBI PubMed ID: 8593633
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Department of Chemistry, Carlsberg Laboratory, Gamle Carlsberg Vej 10, DK-2500 Valby, Copenhagen, Denmark, Department of Chemistry, Simon Fraser University, Burnaby, B.C. V5A 1S6, Canada
  Methods: NMR, conformation analysis
  
   
  
  Streptococcus sp. A
  CSDB ID 8406 (all data & tools)

Show legend Show as text

Structure type: oligomer
Trivial name: part of the cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_133754,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_225177,IEDB_885823

• Article ID: 818
  Hoog C, Rotondo A, Johnston BD, Pinto BM "Synthesis and conformational analysis of a pentasaccharide corresponding to the cell-wall polysaccharide of the group A Streptococcus" - Carbohydrate Research 337(21-23) (2002) 2023-2036
  

  The synthesis and conformational analysis of a pentasaccharide corresponding to a fragment of the cell-wall polysaccharide (CWPS) of the bacteria Streptococcus Group A are described. The polysaccharide consists of alternating α-(1→2)- and α-(1→3)-linked L- rhamnopyranose (Rhap) residues with branching 2-acetamido-2-deoxy-D-glucopyranose (GlcpNAc) residues linked β-(1→3) to alternate rhamnose rings. The pentasaccharide is of interest as a possible terminal unit on the CWPS, for use in a vaccine. The syntheses employed a trichloroacetimidate glycosyl donor. Molecular dynamics (MD) calculations of the pentasaccharide with the force fields CVFF and PARM22, both in gas phase and with explicit water present, gave different predictions for the flexibility and preferred conformational space. Metropolis Monte Carlo (MMC) calculations with the HSEA force field were also performed. Experimental data were obtained from 1D transient NOE measurements. Complete build-up curves were compared to those obtained by full relaxation matrix calculations in order to derive a model of the conformation. Overall, the best fit between experimental and calculated data was obtained with MMC simulations using the HSEA force field. Molecular dynamics and MMC simulations of a tetrasaccharide corresponding to the Group A-variant polysaccharide, which differs in structure from Group A in lacking the GlcpNAc residues, were also performed for purposes of comparison

  conformation, synthesis, structure, tetrasaccharide, chemistry, phase, terminal, polysaccharide, Streptococcus, analysis, group, linked, molecular, water, conformational, dynamics, molecular dynamics, bacteria, cell wall, conformational analysis, calculation, fragment, pentasaccharide, rhamnose, glycosyl, comparison, measurement, vaccine, experimental, simulation, NOE, relaxation, cell wall polysaccharide, model, order, use, ring, flexibility, force field, HSEA, matrix, Monte Carlo, prediction, transient

  NCBI PubMed ID: 11744630
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: bpinto@sfu.ca
  Institutions: Department of Chemistry, Simon Fraser University, British Columbia, V5A 1S6, Burnaby, Canada
  Methods: NMR-2D
  
   
  
  Streptococcus pneumoniae sp. A
  CSDB ID 2434 (all data & tools)

Show legend Show as text

Structure type: oligomer
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_225177,IEDB_885823

• Article ID: 1361
  Auzanneau FI, Forooghian F, Pinto BM "Efficient, convergent syntheses of oligosaccharide allyl glycosides corresponding to the Streptococcus group A cell-wall polysaccharide" - Carbohydrate Research 291 (1996) 21-41
  

  oligosaccharide, polysaccharide, Streptococcus, group, Oligosaccharides, cell wall, glycosides, cell wall polysaccharide, glycoside, allyl, chemical glycosylation

  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada
  
   
  
  Streptococcus pneumoniae A
  CSDB ID 6447 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 2209
  Reimer KB, Harris SL, Varma V, Pinto BM "Convergent synthesis of higher-order oligosaccharides corresponding to the cell-wall polysaccharide of the b-hemolytic Streptococci Group A. A branched hexasaccharide hapten" - Carbohydrate Research 228 (1992) 399-414
  

  A convergent synthesis of a hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococci Group A is described. The strategy relies on the preparation of a key branched trisaccharide unit α-L-Rhap-(1→2)-[β-D-GlcpNAc-(1→3)]-α-L-Rhap which functions both as a glycosyl acceptor and donor. The hexasaccharide is obtained after only three glycosylation reactions. This fully functionalized unit can serve, in turn, as a glycosyl acceptor or donor for the synthesis of higher-order structures. Deprotection gives a hexasaccharide for use as a hapten in immunochemical studies. The characterization of all compounds by high resolution 1H- and 13C-n.m.r. spectroscopy is also described.

  NCBI PubMed ID: 1525784
  Publication DOI: 10.1016/0008-6215(92)84133-d
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada
  
   
  
  Streptococcus sp. A
  CSDB ID 116678 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: GAS-PS, GAC, GAC, group A carbohydrate, GAC-PS
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 3869
  Kabanova A, Margarit I, Berti F, Romano MR, Grandi G, Bensi G, Chiarot E, Proietti D, Swennen E, Cappelletti E, Fontani P, Casini D, Adamo R, Pinto V, Skibinski D, Capo S, Buffi G, Gallotta M, Christ WJ, Campbell AS, Pena J, Seeberger PH, Rappuoli R, Costantino P "Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate" - Vaccine 29(1) (2010) 104-114
  

  Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.

  carbohydrate, GAS, Group A Streptococcus, CHO, wt, weight, ip, intraperitoneal, EU, ELISA units

  NCBI PubMed ID: 20870056
  Publication DOI: 10.1016/j.vaccine.2010.09.018
  Journal NLM ID: 8406899
  Publisher: Elsevier
  Correspondence: P. Costantino
  Institutions: Research Center, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy
  Methods: 1H NMR, ELISA, serological methods, immunization, conjugation, MALDI-TOF/TOF MS
  
   
  
  Streptococcus sp. A
  CSDB ID 25298 (all data & tools)
• Article ID: 5188
  Micoli F, Costantino P, Adamo R "Potential targets for next generation anti-microbial glycoconjugate vaccines" - FEMS Microbiology Reviews 42(3) (2018) 388-423
  

  Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines.Recent analysis from WHO/CHO underpins alarming concern towards antibiotic resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyses structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

  carbohydrates, glycoconjugates, vaccines, glycoengineering, antimicrobial resistance

  NCBI PubMed ID: 29547971
  Publication DOI: 10.1093/femsre/fuy011
  Journal NLM ID: 8902526
  Publisher: Oxford University Press
  Correspondence: Roberto Adamo
  Institutions: GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena
  
   
  
  Streptococcus sp. A
  CSDB ID 12699 (all data & tools)
• Article ID: 5428
  Edgar RJ, van Hensbergen VP, Ruda A, Turner AG, Deng P, Le Breton Y, El-Sayed NM, Belew AT, McIver KS, McEwan AG, Morris AJ, Lambeau G, Walker MJ, Rush JS, Korotkov KV, Widmalm G, van Sorge NM, Korotkova N "Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides" - Nature Chemical Biology 15(5) (2019) 463-471
  

  Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A2. Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.

  analysis, gene cluster, cell wall, modification, glycopolymer, rhamnose, streptococcal, Streptococcus pyogenes, phylogenetic

  NCBI PubMed ID: 30936502
  Publication DOI: 10.1038/s41589-019-0251-4
  Journal NLM ID: 101231976
  Publisher: New York, NY: Nature Publishing Group
  Correspondence: nkorotkova@uky.edu; nsorge3@umcutrecht.nl
  Institutions: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA, Callaghan Innovation, Gracefield, Lower Hutt, New Zealand, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands, Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia, Division of Cardiovascular Medicine and the Gill Heart Institute, University of Kentucky, Lexington, KY, USA, Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA, Department of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA, Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA, Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne Sophia Antipolis, France
  Methods: 13C NMR, 1H NMR, NMR-2D, PCR, GC-MS, X-ray, sugar analysis, 31P NMR, genetic methods, alkaline hydrolysis, crystallography, statistical analysis, LC-MS, phylogenetic analysis
  
   
  
  Streptococcus pyogenes, Streptococcus mutans
  CSDB ID 723 (all data & tools)
• Article ID: 6086
  King H, Ajay Castro S, Pohane AA, Scholte CM, Fischetti VA, Korotkova N, Nelson DC, Dorfmueller HC "Molecular basis for recognition of the Group A Carbohydrate backbone by the PlyC streptococcal bacteriophage endolysin" - Biochemical Journal 478(12) (2021) 2385-2397
  

  Endolysins are peptidoglycan (PG) hydrolases that function as part of the bacteriophage (phage) lytic system to release progeny phage at the end of a replication cycle. Notably, endolysins alone can produce lysis without phage infection, which offers an attractive alternative to traditional antibiotics. Endolysins from phage that infect Gram-positive bacterial hosts contain at least one enzymatically active domain (EAD) responsible for hydrolysis of PG bonds and a cell wall binding domain (CBD) that binds a cell wall epitope, such as a surface carbohydrate, providing some degree of specificity for the endolysin. Whilst the EADs typically cluster into conserved mechanistic classes with well-defined active sites, relatively little is known about the nature of the CBDs and only a few binding epitopes for CBDs have been elucidated. The major cell wall components of many streptococci are the polysaccharides that contain the polyrhamnose (pRha) backbone modified with species-specific and serotype-specific glycosyl side chains. In this report, using molecular genetics, microscopy, flow cytometry and lytic activity assays, we demonstrate the interaction of PlyCB, the CBD subunit of the streptococcal PlyC endolysin, with the pRha backbone of the cell wall polysaccharides, Group A Carbohydrate (GAC) and serotype c-specific carbohydrate (SCC) expressed by the Group A Streptococcus and Streptococcus mutans, respectively.

  polysaccharide, cell wall, rhamnose, bacteriophage, Streptococcus pyogenes, endolysin

  NCBI PubMed ID: 34096588
  Publication DOI: 10.1042/BCJ20210158
  Journal NLM ID: 2984726R
  Publisher: London, UK : Published by Portland Press on behalf of the Biochemical Society
  Correspondence: Helge C. Dorfmueller
  Institutions: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, U.S.A, Division of Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee, U.K, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, U.S.A., Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, U.S.A., Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, U.S.A
  Methods: SDS-PAGE, MD simulations, genetic methods, microscopy, binding assays, FACS assay, molecular docking, blotting, lysis assay
  
   
  
  Streptococcus sp. A
  CSDB ID 10882 (all data & tools)
• Article ID: 6112
  Micoli F, Alfini R, Di Benedetto R, Necchi F, Schiavo F, Mancini F, Carducci M, Oldrini D, Pitirollo O, Gasperini G, Balocchi C, Bechi N, Brunelli B, Piccioli D, Adamo R "Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models" - Frontiers in Immunology 12 (2021) 719315
  

  Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides. Here, we investigated the impact of saccharide length, density, and attachment site on the immune response elicited by GMMA in animal models, using a variety of structurally diverse polysaccharides from different pathogens (i.e., Neisseria meningitidis serogroup A and C, Haemophilus influenzae type b, and streptococcus Group A Carbohydrate and Salmonella Typhi Vi). Anti-polysaccharide immune response was not affected by the number of saccharides per GMMA particle. However, lower saccharide loading can better preserve the immunogenicity of GMMA as antigen. In contrast, saccharide length needs to be optimized for each specific antigen. Interestingly, GMMA conjugates induced strong functional immune response even when the polysaccharides were linked to sugars on GMMA. We also verified that GMMA conjugates elicit a T-dependent humoral immune response to polysaccharides that is strictly dependent on the nature of the polysaccharide. The results obtained are important to design novel glycoconjugate vaccines using GMMA as carrier and support the development of multicomponent glycoconjugate vaccines where GMMA can play the dual role of carrier and antigen. In addition, this work provides significant insights into the mechanism of action of glycoconjugates.

  polysaccharide, vaccine, glycoconjugate, GMMA, carrier protein

  NCBI PubMed ID: 34594333
  Publication DOI: 10.3389/fimmu.2021.719315
  Journal NLM ID: 101560960
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: Francesca Micoli
  Institutions: GSK Vaccines Institute for Global Health (GVGH), Siena, Italy, GSK, Research Centre, Siena, Italy
  Methods: chemical analysis, ELISA, biological assays, HPAEC-PAD, immunization, conjugation, HPLC-SEC, reductive amination, RP-UPLC
  
   
  
  Streptococcus pyogenes
  CSDB ID 9699 (all data & tools)
• Article ID: 6288
  Palmieri E, Kis Z, Ozanne J, Di Benedetto R, Ricchetti B, Massai L, Carducci M, Oldrini D, Gasperini G, Aruta MG, Rossi O, Kontoravdi C, Shah N, Mawas F, Micoli F "GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus" - Vaccines 10(7) (2022) 1034
  

  Group A Streptococcus (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM197; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM197 in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM197, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM197. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden.

  vaccine, glycoconjugate, Group A Streptococcus, GMMA, Group A Carbohydrate

  NCBI PubMed ID: 35891202
  Publication DOI: 10.3390/vaccines10071034
  Journal NLM ID: 101629355
  Publisher: Basel, Switzerland: MDPI AG
  Correspondence: F. Micoli
  Institutions: GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy, The Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK, Department of Chemical and Biological Engineering, The University of Sheffield, Mappin Street, Sheffield S1 3JD, UK, The National Institute for Biological Standards and Control (NIBSC), South Mimms EN6 3QG, UK
  Methods: SDS-PAGE, ELISA, HPAEC-PAD, antibody binding, statistical analysis, oxidation, conjugation, HPLC-SEC, reductive amination, immunogenicity studies, DLS, FACS, genetic engineering, GMMA-technology
  
   
  
  Streptococcus sp. A (GAS51∆M1)
  CSDB ID 8522 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: CH2CH2NH2 or CRM197
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 3869
  Kabanova A, Margarit I, Berti F, Romano MR, Grandi G, Bensi G, Chiarot E, Proietti D, Swennen E, Cappelletti E, Fontani P, Casini D, Adamo R, Pinto V, Skibinski D, Capo S, Buffi G, Gallotta M, Christ WJ, Campbell AS, Pena J, Seeberger PH, Rappuoli R, Costantino P "Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate" - Vaccine 29(1) (2010) 104-114
  

  Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.

  carbohydrate, GAS, Group A Streptococcus, CHO, wt, weight, ip, intraperitoneal, EU, ELISA units

  NCBI PubMed ID: 20870056
  Publication DOI: 10.1016/j.vaccine.2010.09.018
  Journal NLM ID: 8406899
  Publisher: Elsevier
  Correspondence: P. Costantino
  Institutions: Research Center, Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy
  Methods: 1H NMR, ELISA, serological methods, immunization, conjugation, MALDI-TOF/TOF MS
  
   
  
  Streptococcus sp. A
  CSDB ID 25711 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Compound class: peptidoglycan
Contained glycoepitopes: IEDB_127513,IEDB_130648,IEDB_131174,IEDB_133754,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_137473,IEDB_141807,IEDB_142488,IEDB_143254,IEDB_144998,IEDB_146664,IEDB_151531,IEDB_225177,IEDB_885823,IEDB_983931,SB_192

• Article ID: 4166
  Nagaoka M, Muto M, Nomoto K, Matuzaki T, Watanabe T, Yokokura T "Structure of polysaccharide-peptidoglycan complex from the cell wall of Lactobacillus casei YIT9018" - Journal of Biochemistry 108 (1990) 568-571
  

  The isolation and analysis of the polysaccharide-peptidoglycan complexes of Lactobacillus casei YIT9018 are presented. Two polysaccharide-peptidoglycan complexes, PS-PG1 and PS-PG2, were solubilized from the heat-killed cell by treatment with N-acetylmuramidase. PS-PG1 was composed of glucose, rhamnose, and small amount of galactose and glucosamine. PS-PG2 was composed of glucose, rhamnose, galactosamine, and glucosamine. The ratio by weight of these fractions was about 1:8. PS-PG2 was analyzed in detail. Smith degradation and deamination of this complex yielded oligosaccharide units. The results of methylation analysis of these units and intact PS-PG2 led to the most probable structure of PS-PG2: (formula; see text)

  NCBI PubMed ID: 2292584
  Journal NLM ID: 0376600
  Publisher: Japanese Biochemical Society
  Institutions: Yakult Central Institute for Microbiological Research, Tokyo
  Methods: gel filtration, 1H NMR, methylation, GLC-MS, partial acid hydrolysis, Smith degradation, deamination
  
   
  
  Lactobacillus casei YIT 9018
  CSDB ID 132599 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 5188
  Micoli F, Costantino P, Adamo R "Potential targets for next generation anti-microbial glycoconjugate vaccines" - FEMS Microbiology Reviews 42(3) (2018) 388-423
  

  Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines.Recent analysis from WHO/CHO underpins alarming concern towards antibiotic resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyses structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

  carbohydrates, glycoconjugates, vaccines, glycoengineering, antimicrobial resistance

  NCBI PubMed ID: 29547971
  Publication DOI: 10.1093/femsre/fuy011
  Journal NLM ID: 8902526
  Publisher: Oxford University Press
  Correspondence: Roberto Adamo
  Institutions: GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena
  
   
  
  Streptococcus sp. A
  CSDB ID 12699 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: GAC
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 5428
  Edgar RJ, van Hensbergen VP, Ruda A, Turner AG, Deng P, Le Breton Y, El-Sayed NM, Belew AT, McIver KS, McEwan AG, Morris AJ, Lambeau G, Walker MJ, Rush JS, Korotkov KV, Widmalm G, van Sorge NM, Korotkova N "Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides" - Nature Chemical Biology 15(5) (2019) 463-471
  

  Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A2. Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase. We detected the presence of glycerol phosphate in the GAC, as well as the serotype c carbohydrate from Streptococcus mutans, which depended on the presence of the respective gacH homologs. Finally, nuclear magnetic resonance analysis of GAC confirmed that glycerol phosphate is attached to approximately 25% of the GAC N-acetylglucosamine side-chains at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.

  analysis, gene cluster, cell wall, modification, glycopolymer, rhamnose, streptococcal, Streptococcus pyogenes, phylogenetic

  NCBI PubMed ID: 30936502
  Publication DOI: 10.1038/s41589-019-0251-4
  Journal NLM ID: 101231976
  Publisher: New York, NY: Nature Publishing Group
  Correspondence: nkorotkova@uky.edu; nsorge3@umcutrecht.nl
  Institutions: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA, Callaghan Innovation, Gracefield, Lower Hutt, New Zealand, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands, Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia, Division of Cardiovascular Medicine and the Gill Heart Institute, University of Kentucky, Lexington, KY, USA, Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA, Department of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA, Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA, Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne Sophia Antipolis, France
  Methods: 13C NMR, 1H NMR, NMR-2D, PCR, GC-MS, X-ray, sugar analysis, 31P NMR, genetic methods, alkaline hydrolysis, crystallography, statistical analysis, LC-MS, phylogenetic analysis
  
   
  
  Streptococcus pyogenes 5448 WT, Streptococcus pyogenes 5448ΔgacH:pgacH, Streptococcus mutans SMUΔsccH:psccH, Streptococcus mutans SMU WT
  CSDB ID 1003 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit ; n=1-3
Aglycon: (->1)(CH2)2N3 (2-azidoethyl)
Trivial name: GAS-PS
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 5806
  Li R, Yu H, Chen X "Recent progress in chemical synthesis of bacterial surface glycans" - Current Opinion in Chemical Biology 58 (2020) 121-136
  

  With the continuing advancement of carbohydrate chemical synthesis, bacterial glycomes have become increasingly attractive and accessible synthetic targets. Although bacteria also produce carbohydrate-containing secondary metabolites, our review here will cover recent chemical synthetic efforts on bacterial surface glycans. The obtained compounds are excellent candidates for the development of improved structurally defined glycoconjugate vaccines to combat bacterial infections. They are also important probes for investigating glycan–protein interactions. Glycosylation strategies applied for the formation of some challenging glycosidic bonds of various uncommon sugars in a number of recently synthesized bacterial surface glycans are highlighted.

  synthesis, carbohydrate, glycosyltransferase, glycoconjugate vaccine, Bacterial glycan

  NCBI PubMed ID: 32920523
  Publication DOI: 10.1016/j.cbpa.2020.08.003
  Journal NLM ID: 9811312
  Publisher: London: Elsevier
  Correspondence: Chen Xi
  Institutions: Department of Chemistry, University of California Davis, Davis, CA, USA
  
   
  
  Streptococcus sp. A
  CSDB ID 5121 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: ceramide phosphoinositol glycan core (CPI-GC)
Compound class: LPG
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_127513,IEDB_131174,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_140630,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_143254,IEDB_144993,IEDB_144998,IEDB_145003,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_167070,IEDB_167188,IEDB_174332,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983931,SB_173,SB_192,SB_7

• Article ID: 5942
  Heiss C, Wang Z, Azadi P, Fichrova RN, Singh BN "Novel structural features of the immunocompetent ceramide phospho-inositol glycan core from Trichomonas vaginalis" - Carbohydrate Research 419 (2016) 51-59
  

  The ceramide phosphoinositol glycan core (CPI-GC) of the lipophosphoglycan of Trichomonas vaginalis is a major virulent factor of this common genitourinary parasite. While its carbohydrate composition has been reported before, its structure has remained largely unknown. We isolated the glycan portions of CPI-GC by nitrous acid deamination and hydrofluoric acid treatment and investigated their structures by methylation analysis and 1- and 2-D NMR. We found that the α-anomer of galactose is a major constituent of CPI-GC. The β-anomer was found exclusively at the non-reducing end of CPI-GC side chains. Furthermore the data showed that the rhamnan backbone is more complex than previously thought and that the inositol residue at the reducing end is linked to a 4-linked α-glucuronic acid (GlcA) residue. This appears to be the most striking and novel feature of this GPI-anchor type molecule.

  NMR, glycoconjugates, Phospho-inositol glycan core, Trichomonas vaginalis

  NCBI PubMed ID: 26671321
  Publication DOI: 10.1016/j.carres.2015.11.001
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: singhb@upstate.edu; cheiss@uga.edu
  Institutions: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA, Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA
  Methods: 13C NMR, 1H NMR, NMR-2D, methylation, GC-MS, HF treatment, nitrous deamination, enzymatic treatment, HPAE-PAD HPLC
  
   
  
  Trichomonas vaginalis UR1
  CSDB ID 4551 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit ; n=1-3
Aglycon: spacer-ScpA93 protein
Trivial name: glycan epitope (glycotope)
Compound class: cell wall polysaccharide, glycoconjugate
Contained glycoepitopes: IEDB_127513,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 6170
  Zaslona ME, Downey AM, Seeberger PH, Moscovitz O "Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments" - Biochemical Society Transactions 49(5) (2021) 2411-2429
  

  The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.

  carbohydrates, capsular polysaccharides, bacteria, vaccines, synthetic carbohydrate, antibacterial vaccines

  NCBI PubMed ID: 34495299
  Publication DOI: 10.1042/BST20210766
  Journal NLM ID: 7506897
  Correspondence: Oren Moscovitz
  Institutions: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
  
   
  
  Streptococcus sp. A
  CSDB ID 10434 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: rhamnan
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_130695,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 6239
  Guérin H, Kulakauskas S, Chapot-Chartier MP "Structural variations and roles of rhamnose-rich cell wall polysaccharides in Gram-positive bacteria" - Journal of Biological Chemistry 298(10) (2022) 102488
  

  Rhamnose-rich cell wall polysaccharides (Rha-CWPSs) have emerged as crucial cell wall components of numerous Gram-positive, ovoid-shaped bacteria-including streptococci, enterococci, and lactococci-of which many are of clinical or biotechnological importance. Rha-CWPS are composed of a conserved polyrhamnose backbone with side-chain substituents of variable size and structure. Because these substituents contain phosphate groups, Rha-CWPS can also be classified as polyanionic glycopolymers, similar to wall teichoic acids, of which they appear to be functional homologs. Recent advances have highlighted the critical role of these side-chain substituents in bacterial cell growth and division, as well as in specific interactions between bacteria and infecting bacteriophages or eukaryotic hosts. Here, we review the current state of knowledge on the structure and biosynthesis of Rha-CWPS in several ovoid-shaped bacterial species. We emphasize the role played by multicomponent transmembrane glycosylation systems in the addition of side-chain substituents of various sizes as extracytoplasmic modifications of the polyrhamnose backbone. We provide an overview of the contribution of Rha-CWPS to cell wall architecture and biogenesis and discuss current hypotheses regarding their importance in the cell division process. Finally, we sum up the critical roles that Rha-CWPS can play as bacteriophage receptors or in escaping host defenses, roles that are mediated mainly through their side-chain substituents. From an applied perspective, increased knowledge of Rha-CWPS can lead to advancements in strategies for preventing phage infection of lactococci and streptococci in food fermentation and for combating pathogenic streptococci and enterococci.

  polysaccharide, cell wall, rhamnose, teichoic acid, bacteriophage, rhamnan, gram-positive bacteria, antibiotic development, multicomponent glycosylation system, ovoid-shaped, T-C fold glycosyltransferase

  NCBI PubMed ID: 36113580
  Publication DOI: 10.1016/j.jbc.2022.102488
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: M.P. Chapot-Chartier
  Institutions: Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
  
   
  
  Streptococcus pyogenes
  CSDB ID 8471 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: GAC
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_127513,IEDB_130695,IEDB_131174,IEDB_131175,IEDB_131177,IEDB_133754,IEDB_135610,IEDB_135813,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_143254,IEDB_151531,IEDB_2218296,IEDB_225177,IEDB_885823

• Article ID: 6275
  Mahmoud A, Toth I, Stephenson R "Developing an Effective Glycan-Based Vaccine for Streptococcus Pyogenes" - Angewandte Chemie, International Edition 61(11) (2022) e202115342
  

  Streptococcus pyogenes is a primary infective agent that causes approximately 700 million human infections each year, resulting in more than 500 000 deaths. Carbohydrate-based vaccines are proven to be one of the most promising subunit vaccine candidates, as the bacterial glycan pattern(s) are different from mammalian cells and show increased pathogen serotype conservancy than the protein components. In this Review we highlight reverse vaccinology for use in the development of subunit vaccines against S. pyogenes, and report reproducible methods of carbohydrate antigen production, in addition to the structure-immunogenicity correlation between group A carbohydrate epitopes and alternative vaccine antigen carrier systems. We also report recent advances used to overcome hurdles in carbohydrate-based vaccine development.

  Oligosaccharides, glycoconjugates, glycopeptides, immunochemistry, structure-activity relationships

  NCBI PubMed ID: 34935243
  Publication DOI: 10.1002/anie.202115342
  Journal NLM ID: 0370543
  Publisher: Weinheim: Wiley-VCH
  Correspondence: r.stephenson@uq.edu.au
  Institutions: School of Chemistry and Molecular Biosciences, The University of Queensland, Woolloongabba, Australia, School of Pharmacy, The Universitry of Queensland, St Lucia, Australia, Institue for Molecular Biosciences, The University of Queensland, St Lucia, Australia
  
   
  
  Streptococcus pyogenes
  CSDB ID 8508 (all data & tools)