Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: cell-surface polysaccharide, pentaglycosyl phosphate repeating unit cell-surface polysaccharide, rhamnoglucan PSI, PS1, cell-surface polysaccharide PS-I, PSI, PSI repeating unit
Compound class: cell wall polysaccharide, lipoteichoic acid
Contained glycoepitopes: IEDB_136105,IEDB_142488,IEDB_144998,IEDB_145002,IEDB_146664,IEDB_189515,IEDB_189517,IEDB_225177,IEDB_232583,IEDB_232584,IEDB_232585,IEDB_885823,IEDB_983931,SB_192

• Article ID: 3470
  Ganeshapillai J, Vinogradov E, Rousseau J, Weese JS, Monteiro MA "Clostridium difficile cell-surface polysaccharides composed of pentaglycosyl and hexaglycosyl phosphate repeating units" - Carbohydrate Research 343(4) (2008) 703-710
  

  Clostridium difficile is a Gram-positive bacterium that is known to be a cause of enteric diseases in humans. It is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis. Recently, large outbreaks of C. difficile-associated diarrhea have been reported internationally, and there have been reports of increases in severe disease, mortality and relapse rates. At the moment, there is no vaccine against C. difficile, and the medical prevention of C. difficile infection is mostly based on the prophylactic use of antibiotics; however, this has led to an increase in the incidence of the disease. Here, we describe the chemical structure of C. difficile cell-surface polysaccharides. The polysaccharides of three C. difficile strains were structurally analyzed; ribotype 027 (North American pulsotype 1) strain was observed to express two polysaccharides, one was composed of a branched pentaglycosyl phosphate repeating unit: [→4)-α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3]-α-D-Glcp-(1→2)-α-D-Glcp-(1→P] and the other was composed of a hexaglycosyl phosphate repeating unit: [→6)-β-D-Glcp-(1→3)-β-D-GalpNAc-(1→4)-α-D-Glcp-(1→4)-[β-D-Glcp-(1→]-β-D-GalpNAc-(1→3)-α-D-Manp-(1→P]. The latter polysaccharide was also observed to be produced by strains MOH900 and MOH718. The results described here represent the first literature report describing the covalent chemical structures of C. difficile cell-surface polysaccharides, of which PS-II appears to be a regular C. difficile antigen. These C. difficile teichoic-acid-like polysaccharides will be tested as immunogens in vaccine preparations in a rat and horse model.

  Structural characterization, Clostridium difficile, Teichoic-acid polysaccharide

  NCBI PubMed ID: 18237724
  Publication DOI: 10.1016/j.carres.2008.01.002
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: monteiro@uoguelph.ca
  Institutions: Department of Chemistry, University of Guelph, Guelph, ON, Canada N1G 2W1
  Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, 31P NMR, composition analysis
  
   
  
  Clostridium difficile O27
  CSDB ID 22647 (all data & tools)
• Article ID: 4275
  Bertolo L, Boncheff AG, Ma Z, Chen YH, Wakeford T, Friendship RM, Rosseau J, Weese JS, Chu M, Mallozzi M, Vedantam G, Monteiro MA "Clostridium difficile carbohydrates: glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile-ETEC conjugate vaccine" - Carbohydrate Research 354 (2012) 79-86
  

  Clostridium difficile is responsible for severe diarrhea in humans that may cause death. Spores are the infectious form of C. difficile, which germinate into toxin-producing vegetative cells in response to bile acids. Recently, we discovered that C. difficile cells possess three complex polysaccharides (PSs), named PSI, PSII, and PSIII, in which PSI was only associated with a hypervirulent ribotype 027 strain, PSII was hypothesized to be a common antigen, and PSIII was a water-insoluble polymer. Here, we show that (i) C. difficile spores contain, at least in part, a D-glucan, (ii) PSI is not a ribotype 027-unique antigen, (iii) common antigen PSII may in part be present as a low molecular weight lipoteichoic acid, (iv) selective hydrolysis of PSII yields single PSII repeat units, (v) the glycosyl diester-phosphate linkage affords high flexibility to PSII, and (vi) that PSII is immunogenic in sows. Also, with the intent of creating a dual anti-diarrheal vaccine against C. difficile and enterotoxin Escherichia coli (ETEC) infections in humans, we describe the conjugation of PSII to the ETEC-associated LTB enterotoxin.

  conjugate vaccine, glucan, Clostridium difficile, spores, PSI, PSII

  NCBI PubMed ID: 22533919
  Publication DOI: 10.1016/j.carres.2012.03.032
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: monteiro@uoguelph.ca (M.A. Monteiro)
  Institutions: Department of Chemistry, University of Guelph, Guelph, ON, Canada
  Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, SDS-PAGE, sugar analysis, 31P NMR, MD simulations, immunochemical methods, conjugation
  
   
  
  Clostridium difficile 027
  CSDB ID 28310 (all data & tools)
• Article ID: 4378
  Reid CW, Vinogradov E, Li J, Jarrell HC, Logan SM, Brisson JR "Structural characterization of surface glycans from Clostridium difficile" - Carbohydrate Research 354 (2012) 65-73
  

  Whole-cell high-resolution magic angle spinning (HR-MAS) NMR was employed to survey the surface polysaccharides of a group of clinical and environmental isolates of Clostridium difficile. Results indicated that a highly conserved surface polysaccharide profile among all strains studied. Multiple additional peaks in the anomeric region were also observed which prompted further investigation. Structural characterization of the isolated surface polysaccharides from two strains confirmed the presence of the conserved water soluble polysaccharide originally described by Ganeshapillai et al. which was composed of a hexaglycosyl phosphate repeat consisting of [→6)-β-D-Glcp-(1-3)-β-D-GalpNAc-(1-4)-α-D-Glcp-(1-4)-[β-D-Glcp(1-3]-β-D-GalpNAc-(1-3)-α-D-Manp-(1-P→]. In addition, analysis of phenol soluble polysaccharides revealed a similarly conserved lipoteichoic acid (LTA) which could be detected on whole cells by HR-MAS NMR. Conventional NMR and mass spectrometry analysis indicated that the structure of this LTA consisted of the repeat unit [→6)-α-D-GlcpNAc-(1-3)-[→P-6]-α-D-GlcpNAc-(1-2)-D-GroA] where GroA is glyceric acid. The repeating units were linked by a phosphodiester bridge between C-6 of the two GlcNAc residues (6-P-6). A minor component consisted of GlcpN-(1-3) instead of GlcpNAc-(1-3) in the repeat unit. Through a 6-6 phosphodiester bridge this polymer was linked to →6)-β-D-Glcp-(1-6)-β-D-Glcp-(1-6)-β-D-Glcp-(1-1)-Gro, with glycerol (Gro) substituted by fatty acids. This is the first report of the utility of HR-MAS NMR in the examination of surface carbohydrates of Gram positive bacteria and identification of a novel LTA structure from Clostridium difficile.

  capsular polysaccharide, lipoteichoic acid, Clostridium difficile, lipocarbohydrate, High-resolution magic angle spinning (HRMAS) NMR

  NCBI PubMed ID: 22560631
  Publication DOI: 10.1016/j.carres.2012.02.002
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: S.M. Logan
  Institutions: National Research Council-Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON, Canada K1A 0R6
  Methods: 13C NMR, 1H NMR, de-O-acylation, sugar analysis, 31P NMR, HF treatment, CE-MS/MS, HR-MAS NMR
  
   
  
  Clostridium difficile O27
  CSDB ID 28604 (all data & tools)
• Article ID: 4542
  Jiao Y, Ma Z, Hodgins D, Pequegnat B, Bertolo L, Arroyo L, Monteiro MA "Clostridium difficile PSI polysaccharide: synthesis of pentasaccharide repeating block, conjugation to exotoxin B subunit, and detection of natural anti-PSI IgG antibodies in horse serum" - Carbohydrate Research 378 (2013) 15-25
  

  Clostridium difficile is the most common cause of antimicrobial-associated diarrhea in humans and may cause death. Previously, we discovered that C. difficile expresses three polysaccharides, named PSI, PSII, and PSIII. It has now been established that PSII is a conserved antigen abundantly present on the cell-surface and biofilm of C. difficile. In contrast, the expression of PSI and PSIII appears to be stochastic processes. In this work, the total chemical synthesis of the PSI pentasaccharide repeating unit carrying a linker at the reducing end, α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-D-Glcp-(1→O(CH2)5NH2, was achieved by a linear synthesis strategy from four monosaccharide building blocks. The synthesized PSI pentasaccharide was conjugated to a subunit of C. difficile exotoxin B yielding a potential dual C. difficile vaccine. More significantly, sera from healthy horses were shown to contain natural anti-PSI IgG antibodies that detected both the synthetic non-phosphorylated PSI repeat and the native PSI polysaccharide, with a slightly higher recognition of the native PSI polysaccharide.

  vaccine, Clostridium difficile, Anti-PSI IgG antibodies, C. difficile PSI polysaccharide, C. difficile Toxin B conjugate

  NCBI PubMed ID: 23597587
  Publication DOI: 10.1016/j.carres.2013.03.018
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: M.A. Monteiro
  Institutions: Department of Chemistry, University of Guelph, Guelph, ON, Canada
  Methods: 13C NMR, 1H NMR, SDS-PAGE, TLC, ELISA, chemical synthesis, conjugation
  
   
  
  Clostridium difficile O27
  CSDB ID 29214 (all data & tools)
• Article ID: 4572
  Martin CE, Weishaupt MW, Seeberger PH "Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit" - Chemical Communications 47(37) (2011) 10260-10262
  

  Clostridium difficile strain ribotype 027 is a hypervirulent pathogen that is responsible for recent, severe outbreaks of serious nosocomial infections. As a foundation for the development of a preventative carbohydrate-based vaccine, we have synthesized a pentasaccharide cell wall repeating unit from PS-I unique to this strain, by the linear assembly of four monosaccharide building blocks.

  synthesis, repeating unit, pentasaccharide, vaccine, nosocomial infections, Clostridium difficile

  Publication DOI: 10.1039/C1CC13614C
  Journal NLM ID: 9610838
  Publisher: Cambridge: Royal Society of Chemistry
  Correspondence: peter.seeberger@mpikg.mpg.de
  Institutions: Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Muhlenberg 1, 14476 Potsdam, Germany
  Methods: 13C NMR, 1H NMR, chemical synthesis, chemical methods, glycosylation
  
   
  
  Clostridium difficile O27
  CSDB ID 29273 (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
  
   
  
  Clostridium difficile
  CSDB ID 12687 (all data & tools)
• Article ID: 5740
  Campanero-Rhodes MA, Palma AS, Menendez M, Solis D "Microarray Strategies for Exploring Bacterial Surface Glycans and Their Interactions With Glycan-Binding Proteins" - Frontiers in Microbiology 10 (2020) 2909
  

  Bacterial surfaces are decorated with distinct carbohydrate structures that may substantially differ among species and strains. These structures can be recognized by a variety of glycan-binding proteins, playing an important role in the bacteria cross-talk with the host and invading bacteriophages, and also in the formation of bacterial microcolonies and biofilms. In recent years, different microarray approaches for exploring bacterial surface glycans and their recognition by proteins have been developed. A main advantage of the microarray format is the inherent miniaturization of the method, which allows sensitive and high-throughput analyses with very small amounts of sample. Antibody and lectin microarrays have been used for examining bacterial glycosignatures, enabling bacteria identification and differentiation among strains. In addition, microarrays incorporating bacterial carbohydrate structures have served to evaluate their recognition by diverse host/phage/bacterial glycan-binding proteins, such as lectins, effectors of the immune system, or bacterial and phagic cell wall lysins, and to identify antigenic determinants for vaccine development. The list of samples printed in the arrays includes polysaccharides, lipopoly/lipooligosaccharides, (lipo)teichoic acids, and peptidoglycans, as well as sequence-defined oligosaccharide fragments. Moreover, microarrays of cell wall fragments and entire bacterial cells have been developed, which also allow to study bacterial glycosylation patterns. In this review, examples of the different microarray platforms and applications are presented with a view to give the current state-of-the-art and future prospects in this field.

  antibodies, immune system, lectins, vaccine development, microarrays, bacterial glycans, bacterial interactions

  NCBI PubMed ID: 32010066
  Publication DOI: 10.3389/fmicb.2019.02909
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: Dolores Solis
  Institutions: Instituto de Quimica Fisica Rocasolano, Consejo Superior de Investigaciones Cientificas, Madrid, Spain, Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain, UCIBIO, Department of Chemistry, Faculty of Science and Technology, NOVA University of Lisbon, Lisbon, Portuga
  
   
  
  Clostridium difficile
  CSDB ID 32072 (all data & tools)
• Article ID: 6211
  Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" - Chemical Reviews 122(20) (2022) 15672-15716
  

  Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

  carbohydrates, glycan, glycoconjugate vaccine

  NCBI PubMed ID: 35608633
  Publication DOI: 10.1021/acs.chemrev.2c00021
  Journal NLM ID: 2985134R
  Publisher: Chem Rev
  Correspondence: J. Codée ; R. Adamo
  Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
  
   
  
  Clostridioides difficile
  CSDB ID 20886 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: 5-amino-pentanyl
Trivial name: PS1, cell-surface polysaccharide PS-I
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_136105,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_189515,IEDB_189517,IEDB_225177,IEDB_232583,IEDB_232584,IEDB_232585,IEDB_885823,IEDB_983931,SB_192

• Article ID: 4542
  Jiao Y, Ma Z, Hodgins D, Pequegnat B, Bertolo L, Arroyo L, Monteiro MA "Clostridium difficile PSI polysaccharide: synthesis of pentasaccharide repeating block, conjugation to exotoxin B subunit, and detection of natural anti-PSI IgG antibodies in horse serum" - Carbohydrate Research 378 (2013) 15-25
  

  Clostridium difficile is the most common cause of antimicrobial-associated diarrhea in humans and may cause death. Previously, we discovered that C. difficile expresses three polysaccharides, named PSI, PSII, and PSIII. It has now been established that PSII is a conserved antigen abundantly present on the cell-surface and biofilm of C. difficile. In contrast, the expression of PSI and PSIII appears to be stochastic processes. In this work, the total chemical synthesis of the PSI pentasaccharide repeating unit carrying a linker at the reducing end, α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-D-Glcp-(1→O(CH2)5NH2, was achieved by a linear synthesis strategy from four monosaccharide building blocks. The synthesized PSI pentasaccharide was conjugated to a subunit of C. difficile exotoxin B yielding a potential dual C. difficile vaccine. More significantly, sera from healthy horses were shown to contain natural anti-PSI IgG antibodies that detected both the synthetic non-phosphorylated PSI repeat and the native PSI polysaccharide, with a slightly higher recognition of the native PSI polysaccharide.

  vaccine, Clostridium difficile, Anti-PSI IgG antibodies, C. difficile PSI polysaccharide, C. difficile Toxin B conjugate

  NCBI PubMed ID: 23597587
  Publication DOI: 10.1016/j.carres.2013.03.018
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: M.A. Monteiro
  Institutions: Department of Chemistry, University of Guelph, Guelph, ON, Canada
  Methods: 13C NMR, 1H NMR, SDS-PAGE, TLC, ELISA, chemical synthesis, conjugation
  
   
  
  Clostridium difficile O27
  CSDB ID 29589 (all data & tools)
• Article ID: 4572
  Martin CE, Weishaupt MW, Seeberger PH "Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit" - Chemical Communications 47(37) (2011) 10260-10262
  

  Clostridium difficile strain ribotype 027 is a hypervirulent pathogen that is responsible for recent, severe outbreaks of serious nosocomial infections. As a foundation for the development of a preventative carbohydrate-based vaccine, we have synthesized a pentasaccharide cell wall repeating unit from PS-I unique to this strain, by the linear assembly of four monosaccharide building blocks.

  synthesis, repeating unit, pentasaccharide, vaccine, nosocomial infections, Clostridium difficile

  Publication DOI: 10.1039/C1CC13614C
  Journal NLM ID: 9610838
  Publisher: Cambridge: Royal Society of Chemistry
  Correspondence: peter.seeberger@mpikg.mpg.de
  Institutions: Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Muhlenberg 1, 14476 Potsdam, Germany
  Methods: 13C NMR, 1H NMR, chemical synthesis, chemical methods, glycosylation
  
   
  
  Clostridium difficile O27
  CSDB ID 29646 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: 5-amino-pentyl, spacer-CRM197
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_136105,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_189515,IEDB_189517,IEDB_225177,IEDB_232583,IEDB_232584,IEDB_232585,IEDB_885823,IEDB_983931,SB_192

• Article ID: 6211
  Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" - Chemical Reviews 122(20) (2022) 15672-15716
  

  Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

  carbohydrates, glycan, glycoconjugate vaccine

  NCBI PubMed ID: 35608633
  Publication DOI: 10.1021/acs.chemrev.2c00021
  Journal NLM ID: 2985134R
  Publisher: Chem Rev
  Correspondence: J. Codée ; R. Adamo
  Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
  
   
  
  Clostridioides difficile
  CSDB ID 20889 (all data & tools)