Show legend Show as text

Structure type: polymer chemical repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_240849

• Article ID: 366
  Sau S, Lee CY "Cloning of type 8 capsule genes and analysis of gene clusters for the production of different capsular polysaccharides in Staphylococcus aureus" - Journal of Bacteriology 178(7) (1996) 2118-2126
  

  Eleven serotypes of capsular polysaccharide from Staphylococcus aureus have been reported. We have previously cloned a cluster of type 1 capsule (cap1) genes responsible for type 1 capsular polysaccharide biosynthesis in S. aureus M. To clone the type 8 capsule (cap8) genes, a plasmid library of type 8 strain Becker was screened with a labelled DNA fragment containing the cap1 genes under low-stringency conditions. One recombinant plasmid containing a 14-kb insert was chosen for further study and found to complement 14 of the 18 type 8 capsule-negative (Cap8-) mutants used in the study. Additional library screening, subcloning, and complementation experiments showed that all of the 18 Cap8- mutants were complemented by DNA fragments derived from a 20.5-kb contiguous region of the Becker chromosome. The mutants were mapped into six complementation groups, indicating that the cap8 genes are clustered. By Southern hybridization analyses under high-stringency conditions, we found that DNA fragments containing the cap8 gene cluster show extensive homology with all 17 strains tested, including type 1 strains. By further Southern analyses and cloning of the cap8-related homolog from strain M, we show that strain M carries an additional capsule gene cluster different from the cap1 gene cluster. In addition, by using DNA fragments containing different regions of the cap8 gene cluster as probes to hybridize DNA from different strains, we found that the central region of the cap8 gene cluster hybridizes only to DNAs from certain strains tested whereas the flanking regions hybridize to DNAs of all strains tested. Thus, the cap8 gene clusters and its closely related homologs are likely to have organizations similar to those of the encapsulation genes of other bacterial systems.

  analysis, capsular polysaccharides, cloning, type, gene cluster, capsule, Staphylococcus aureus

  NCBI PubMed ID: 8606192
  Journal NLM ID: 2985120R
  Publisher: American Society for Microbiology
  Correspondence: clee@kumc.edu
  Institutions: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160
  Methods: genetic methods
  
   
  
  Staphylococcus aureus CP5
  CSDB ID 8117 (all data & tools)
• Article ID: 583
  Fattom AI, Horwith G, Fuller S, Propst M, Naso R "Development of StaphVAX, a polysaccharide conjugate vaccine against S. aureus infection: from the lab bench to phase III clinical trials" - Vaccine 22(7) (2004) 880-887
  

  Staphylococcus aureus is the most common nosocomial pathogen and is responsible for approximately one-third of hospital-acquired bacteremias. The emergence of strains with multidrug resistance, including resistance to vancomycin, the antibiotic of last resort, presents the medical community with a major public health problem. Alternative therapies, including immunotherapy, have been in development for several decades. The discovery of S. aureus capsular polysaccharides from clinical isolates, and their importance to pathogenicity via antiphagocytic activity, opened a new window of opportunity for development of vaccines and immunotherapy against this pathogen. A conjugate vaccine, StaphVAX that includes the two most prevalent capsular polysaccharides, types 5 and 8, coupled to a carrier protein efficient in promoting a Th2 response, was developed. In a recent phase III clinical study in hemodialysis patients, StaphVAX was shown to prevent S. aureus bacteremia for up to 10 months following a single immunization. The history, epidemiology, serology, and development of StaphVAX, including preclinical and clinical studies demonstrating efficacy are described in this review.

  polysaccharide, Staphylococcus, conjugate vaccine

  NCBI PubMed ID: 15040941
  Journal NLM ID: 8406899
  Publisher: Elsevier
  Correspondence: afattom@nabi.com
  Institutions: NABI Biopharmaceuticals, 12280 Wilkins Avenue, Rockville, MD 20852, USA
  Methods: ELISA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 9595 (all data & tools)
• Article ID: 1373
  Bhasin N, Albus A, Michon F, Livolsi PJ, Park JS, Lee JC "Identification of a gene essential for O-acetylation of the Staphylococcus aureus type 5 capsular polysaccharide" - Molecular Microbiology 27(1) (1998) 9-21
  

  gene, capsular, polysaccharide, capsular polysaccharide, identification, type, O-acetylation, Staphylococcus, Staphylococcus aureus

  Journal NLM ID: 8712028
  Publisher: Blackwell Publishing
  Correspondence: jean.lee@channing.harvard.edu
  Institutions: Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical school, Boston, USA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 6259 (all data & tools)
• Article ID: 1394
  Burrows LL, Pigeon KE, Lam JS "Psudomonas aeruginosa B-band lipopolysaccharide genes wbpA and wbpI and their Escherichia coli homologues wecC and wecB are not functionally interchangeable" - FEMS Microbiology Reviews 189 (2000) 135-141
  

  The O antigen unit of Pseudomonas aeruginosa serotype O5 is a complex trisaccharide containing 2-acetamido-3-acetiminido-2,3-dideoxy- L-D-mannuronic acid, 2-acetimido-3-acetimido-2,3-dideoxy-L-D-mannuronic acid, and 2-acetimido-2,6-deoxy-L-D-galactosamine. Specific knockout mutations in the putative UDP-D-N-acetylglucosamine (UDP-D-GlcNAc) epimerase gene, wbpI, or the putative UDP-D-Nacetylmannosamine dehydrogenase gene, wbpA, resulted in strains that no longer produced B-band lipopolysaccharide, confirming the essential roles of these genes in B-band O antigen synthesis. Despite approximately 50% similarity of wbpI and wbpA to the Escherichia coli genes wecB (rffE) and wecC (rffD) involved in enterobacterial common antigen synthesis, cross-complementation experiments were not successful. These results imply that the P. aeruginosa UDP-D-GlcNAc precursor may be di-N-acetylated prior to further modification, preventing the E. coli enzymes from recognizing it as a substrate.

  Lipopolysaccharide, gene, B-band, Escherichia, Escherichia coli, WbpA, WbpI

  NCBI PubMed ID: 10930727
  Journal NLM ID: 8902526
  Publisher: Oxford University Press
  Correspondence: jlam@uoguelph.ca
  Institutions: Department of Microbiology, University of Guelph, Gueph, Canada
  Methods: genetic methods
  
   
  
  Staphylococcus aureus CP5
  CSDB ID 6634 (all data & tools)
• Article ID: 1519
  Jones C "NMR assays for carbohydrate-based vaccines" - Journal of Pharmaceutical and Biomedical Analysis 38(5) (2005) 840-850
  

  Antibodies against the cell surface carbohydrates of many microbial pathogens protect against infection. This was initially exploited by the development of purified polysaccharide vaccines, but glycoconjugate vaccines, in which the cell surface carbohydrate of a microbial pathogen is covalently attached to an appropriate carrier protein, are proving the most effective means to generate this protective immunity. Carbohydrate-based vaccines against Haemophilus influenzae Type b, Neisseria meningitidis, Streptococcus pneumoniae and Salmonella enterica serotype Typhi (S. Typhi) are already licensed, and many similar products are in various stages of development. For many of these vaccines, biological assays are not available or are inappropriate and NMR spectroscopy is proving a valuable tool for the characterisation and quality control of existing and novel products. This review highlights some of the areas in which NMR spectroscopy is currently used, and where further developments may be expected.

  capsular polysaccharide, O-acetylation, pneumonia, glycoconjugate, meningitis, carbohydrate-based vaccines, identity, typhoid

  NCBI PubMed ID: 16087046
  Publication DOI: 10.1016/j.jpba.2005.01.044
  Journal NLM ID: 8309336
  Publisher: London: Elsevier
  Institutions: Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, UK
  Methods: NMR
  
   
  
  Staphylococcus aureus 5
  CSDB ID 10378 (all data & tools)
• Article ID: 3295
  Lee JC, Xu S, Albus A, Livolsi PJ "Genetic analysis of type 5 capsular polysaccharide expression by Staphylococcus aureus" - Journal of Bacteriology 176(16) (1994) 4883-4889
  

  Capsules are produced by over 90% of Staphylococcus aureus strains, and approximately 25% of clinical isolates express type 5 capsular polysaccharide (CP5). We mutagenized the type 5 strain Reynolds with Tn918 to target genes involved in CP5 expression. From a capsule-deficient mutant, we cloned into a cosmid vector an approximately 26-kb EcoRI fragment containing the transposon insertion. In the absence of tetracycline selection, Tn918 was spontaneously excised, thereby resulting in a plasmid containing 9.4 kb of S. aureus DNA flanking the Tn918 insertion site. The 9.4-kb DNA fragment was used to screen a cosmid library prepared from the wild-type strain. Positive colonies were identified by colony hybridization, and a restriction map of one clone (pJCL19 with an approximately 34-kb insert) carrying the putative capsule gene region was constructed. Fragments of pJCL19 were used to probe genomic DNA digests from S. aureus strains of different capsular serotypes. Fragments on the ends of the cloned DNA hybridized to fragments of similar sizes in most of the strains examined. Blots hybridized to two fragments flanking the central region of the cloned DNA showed restriction fragment length polymorphism. A centrally located DNA fragment hybridized only to DNA from capsular types 2, 4, and 5. DNA from pJCL19 was subcloned to a shuttle vector for complementation studies. A 6.2-kb EcoRI-ClaI fragment complemented CP5 expression in a capsule-negative mutant derived by mutagenesis with ethyl methanesulfonate. These experiments provide the necessary groundwork for identifying genes involved in CP5 expression by S. aureus.

  genetic, clinical, expression, gene, genetics, DNA, strain, capsular, polysaccharide, serotype, analysis, capsular polysaccharide, Serotypes, type, mutant, region, insertion, plasmid, capsule, Staphylococcus, Staphylococcus aureus, fragment, site, clone, PDF, capsules, selection, polymorphism

  NCBI PubMed ID: 805001
  Journal NLM ID: 2985120R
  Publisher: American Society for Microbiology
  Institutions: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  Methods: serological methods, genetic methods
  
   
  
  Staphylococcus aureus 5
  CSDB ID 22492 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Trivial name: CP5
Compound class: EPS, O-polysaccharide, CPS
Contained glycoepitopes: IEDB_240847,IEDB_240849

• Article ID: 583
  Fattom AI, Horwith G, Fuller S, Propst M, Naso R "Development of StaphVAX, a polysaccharide conjugate vaccine against S. aureus infection: from the lab bench to phase III clinical trials" - Vaccine 22(7) (2004) 880-887
  

  Staphylococcus aureus is the most common nosocomial pathogen and is responsible for approximately one-third of hospital-acquired bacteremias. The emergence of strains with multidrug resistance, including resistance to vancomycin, the antibiotic of last resort, presents the medical community with a major public health problem. Alternative therapies, including immunotherapy, have been in development for several decades. The discovery of S. aureus capsular polysaccharides from clinical isolates, and their importance to pathogenicity via antiphagocytic activity, opened a new window of opportunity for development of vaccines and immunotherapy against this pathogen. A conjugate vaccine, StaphVAX that includes the two most prevalent capsular polysaccharides, types 5 and 8, coupled to a carrier protein efficient in promoting a Th2 response, was developed. In a recent phase III clinical study in hemodialysis patients, StaphVAX was shown to prevent S. aureus bacteremia for up to 10 months following a single immunization. The history, epidemiology, serology, and development of StaphVAX, including preclinical and clinical studies demonstrating efficacy are described in this review.

  polysaccharide, Staphylococcus, conjugate vaccine

  NCBI PubMed ID: 15040941
  Journal NLM ID: 8406899
  Publisher: Elsevier
  Correspondence: afattom@nabi.com
  Institutions: NABI Biopharmaceuticals, 12280 Wilkins Avenue, Rockville, MD 20852, USA
  Methods: ELISA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 9595 (all data & tools)
• Article ID: 1373
  Bhasin N, Albus A, Michon F, Livolsi PJ, Park JS, Lee JC "Identification of a gene essential for O-acetylation of the Staphylococcus aureus type 5 capsular polysaccharide" - Molecular Microbiology 27(1) (1998) 9-21
  

  gene, capsular, polysaccharide, capsular polysaccharide, identification, type, O-acetylation, Staphylococcus, Staphylococcus aureus

  Journal NLM ID: 8712028
  Publisher: Blackwell Publishing
  Correspondence: jean.lee@channing.harvard.edu
  Institutions: Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical school, Boston, USA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 6259 (all data & tools)
• Article ID: 1519
  Jones C "NMR assays for carbohydrate-based vaccines" - Journal of Pharmaceutical and Biomedical Analysis 38(5) (2005) 840-850
  

  Antibodies against the cell surface carbohydrates of many microbial pathogens protect against infection. This was initially exploited by the development of purified polysaccharide vaccines, but glycoconjugate vaccines, in which the cell surface carbohydrate of a microbial pathogen is covalently attached to an appropriate carrier protein, are proving the most effective means to generate this protective immunity. Carbohydrate-based vaccines against Haemophilus influenzae Type b, Neisseria meningitidis, Streptococcus pneumoniae and Salmonella enterica serotype Typhi (S. Typhi) are already licensed, and many similar products are in various stages of development. For many of these vaccines, biological assays are not available or are inappropriate and NMR spectroscopy is proving a valuable tool for the characterisation and quality control of existing and novel products. This review highlights some of the areas in which NMR spectroscopy is currently used, and where further developments may be expected.

  capsular polysaccharide, O-acetylation, pneumonia, glycoconjugate, meningitis, carbohydrate-based vaccines, identity, typhoid

  NCBI PubMed ID: 16087046
  Publication DOI: 10.1016/j.jpba.2005.01.044
  Journal NLM ID: 8309336
  Publisher: London: Elsevier
  Institutions: Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, UK
  Methods: NMR
  
   
  
  Staphylococcus aureus 5
  CSDB ID 10378 (all data & tools)
• Article ID: 1520
  Jones C "Revised structures for the capsular polysaccharides from Staphylococcus aureus types 5 and 8, components of novel glycoconjugate vaccines" - Carbohydrate Research 340(6) (2005) 1097-1106
  

  Glycoconjugate vaccines based on the capsular polysaccharides (CPSs) from Staphylococcus aureus serotypes 5 and 8 conjugated to genetically detoxified recombinant exoprotein A (rEPA) from Pseudomonas aeruginosa have been shown, in Phase 3 clinical trials, to elicit a strong bactericidal immune response in end-stage renal disease patients. Such vaccines have the potential to reduce morbidity and mortality due to methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-acquired infection. The serotype 5 and 8 polysaccharides have been fully characterized by NMR spectroscopy and full structural analyses carried out. Published structures were found incorrect and the revised structures of the repeat units of the two polysaccharides are: [carbohydrate structure: see text]. Resonances indicative of the presence of peptidoglycan were observed in the spectra of both CPSs, consistent with reports that the CPS is covalently linked to peptidoglycan.

  polysaccharide, NMR spectroscopy, capsule, Staphylococcus aureus, peptidoglycan, conjugate vaccine

  NCBI PubMed ID: 15797125
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, UK
  Methods: NMR, sugar analysis, determination of absolute configuration
  
   
  
  Staphylococcus aureus 5
  CSDB ID 10062 (all data & tools)
• Article ID: 2168
  Moreau M, Richards JC, Fournier JM, Byrd RA, Karakawa WW, Vann WF "Structure of the type 5 capsular polysaccharide of Staphylococcus aureus" - Carbohydrate Research 201(2) (1990) 285-297
  

  The Staphylococcus aureus type 5 capsular polysaccharide is composed of 2-acetamido-2-deoxy-l-fucose (1 part), 2-acetamido-2-deoxy-d-fucose (1 part), and 2-acetamido-2-deoxy-d-mannuronic acid (1 part). On the basis of methylation analysis, optical rotation, high-field one- and two-dimensional 1H- and 13C-n.m.r. experiments, and selective cleavage with 70% aqueous hydrogen fluoride, the polysaccharide was found to be a partially O-acetylated (50%) polymer of the repeating trisaccharide unit, [→4)-3-O-Ac-β-d-ManpNAcA-(1→4)-α-l-FucpNAc-(1→3)-β-d-FucpNAc-(1→]n.

  NCBI PubMed ID: 2224883
  Publication DOI: 10.1016/0008-6215(90)84244-O
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Office of Biologics Research and Review, Food and Drug Administration, Bethesda, MD, USA, U.S.A., Division of Biological Sciences, National Research Council of Canada, Ottawa K1A OR6 Canada, Unité du Cholerá et des Vibrions, Institut Pasteur, F-75724 Paris France
  Methods: gel filtration, 13C NMR, 1H NMR, methylation, GLC-MS, GLC, HF treatment
  
   
  
  Staphylococcus aureus 5
  CSDB ID 115941 (all data & tools)
• Article ID: 3295
  Lee JC, Xu S, Albus A, Livolsi PJ "Genetic analysis of type 5 capsular polysaccharide expression by Staphylococcus aureus" - Journal of Bacteriology 176(16) (1994) 4883-4889
  

  Capsules are produced by over 90% of Staphylococcus aureus strains, and approximately 25% of clinical isolates express type 5 capsular polysaccharide (CP5). We mutagenized the type 5 strain Reynolds with Tn918 to target genes involved in CP5 expression. From a capsule-deficient mutant, we cloned into a cosmid vector an approximately 26-kb EcoRI fragment containing the transposon insertion. In the absence of tetracycline selection, Tn918 was spontaneously excised, thereby resulting in a plasmid containing 9.4 kb of S. aureus DNA flanking the Tn918 insertion site. The 9.4-kb DNA fragment was used to screen a cosmid library prepared from the wild-type strain. Positive colonies were identified by colony hybridization, and a restriction map of one clone (pJCL19 with an approximately 34-kb insert) carrying the putative capsule gene region was constructed. Fragments of pJCL19 were used to probe genomic DNA digests from S. aureus strains of different capsular serotypes. Fragments on the ends of the cloned DNA hybridized to fragments of similar sizes in most of the strains examined. Blots hybridized to two fragments flanking the central region of the cloned DNA showed restriction fragment length polymorphism. A centrally located DNA fragment hybridized only to DNA from capsular types 2, 4, and 5. DNA from pJCL19 was subcloned to a shuttle vector for complementation studies. A 6.2-kb EcoRI-ClaI fragment complemented CP5 expression in a capsule-negative mutant derived by mutagenesis with ethyl methanesulfonate. These experiments provide the necessary groundwork for identifying genes involved in CP5 expression by S. aureus.

  genetic, clinical, expression, gene, genetics, DNA, strain, capsular, polysaccharide, serotype, analysis, capsular polysaccharide, Serotypes, type, mutant, region, insertion, plasmid, capsule, Staphylococcus, Staphylococcus aureus, fragment, site, clone, PDF, capsules, selection, polymorphism

  NCBI PubMed ID: 805001
  Journal NLM ID: 2985120R
  Publisher: American Society for Microbiology
  Institutions: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  Methods: serological methods, genetic methods
  
   
  
  Staphylococcus aureus 5
  CSDB ID 22492 (all data & tools)
• Article ID: 4430
  Ovodov YS "Bacterial capsular antigens. Structural patterns of capsular antigens" - Biochemistry (Moscow) 71(9) (2006) 937-954
  

  Structural patterns of bacterial capsular antigens including capsular polysaccharides and exoglycans are given in this review. In addition, the immunological activity of capsular antigens and their role in type specificity of bacteria are discussed.

  structure, capsular polysaccharides, bacterial capsular antigens, bacterial exoglycans, immunological activity, type specificity

  NCBI PubMed ID: 17009947
  Publication DOI: 10.1134/S000629790609001X
  Journal NLM ID: 0376536
  Publisher: Nauka/Interperiodica
  Correspondence: ovoys@physiol.komisc.ru
  Institutions: Institute of Physiology, Komi Science Center, Urals Branch of the Russian Academy of Sciences, Syktyvkar 167982, Russia
  
   
  
  Staphylococcus aureus 5
  CSDB ID 28735 (all data & tools)
• Article ID: 4883
  Weidenmaier C, Lee JC "Structure and Function of Surface Polysaccharides of Staphylococcus aureus" - Current Topics in Medicinal Chemistry (2016) 1-37
  

  The major surface polysaccharides of Staphylococcus aureus include the capsular polysaccharide (CP), cell wall teichoic acid (WTA), and polysaccharide intercellular adhesin/poly-β(1-6)-N-acetylglucosamine (PIA/PNAG). These glycopolymers are important components of the staphylococcal cell envelope, but none of them is essential to S. aureus viability and growth in vitro. The overall biosynthetic pathways of CP, WTA, and PIA/PNAG have been elucidated, and the functions of most of the biosynthetic enzymes have been demonstrated. Because S. aureus CP and WTA (but not PIA/PNAG) utilize a common cell membrane lipid carrier (undecaprenyl-phosphate) that is shared by the peptidoglycan biosynthesis pathway, there is evidence that these processes are highly integrated and temporally regulated. Regulatory elements that control glycopolymer biosynthesis have been described, but the cross talk that orchestrates the biosynthetic pathways of these three polysaccharides remains largely elusive. CP, WTA, and PIA/PNAG each play distinct roles in S. aureus colonization and the pathogenesis of staphylococcal infection. However, they each promote bacterial evasion of the host immune defences, and WTA is being explored as a target for antimicrobial therapeutics. All the three glycopolymers are viable targets for immunotherapy, and each (conjugated to a carrier protein) is under evaluation for inclusion in a multivalent S. aureus vaccine. Future research findings that increase our understanding of these surface polysaccharides, how the bacterial cell regulates their expression, and their biological functions will likely reveal new approaches to controlling this important bacterial pathogen.

  structure, Pathogenesis, capsular polysaccharide, polysaccharides, Staphylococcus aureus, Enzymes, teichoic acid, vaccine, surface polysaccharide, peptidoglycan biosynthesis

  NCBI PubMed ID: 26728067
  Publication DOI: 10.1007/82_2015_5018
  Journal NLM ID: 101119673
  Publisher: Bentham Science Publishers
  Correspondence: chrisweidenmaier@googlemail.com; JCLEE@BWH.HARVARD.EDU
  Institutions: Interfaculty Institute for Microbiology and Infection Medicine Tubingen, University of Tubingen and German Center for Infection Research, Tubingen, Germany, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 11249 (all data & tools)
• Article ID: 4925
  Sanapala SR, Kulkarni SS "Expedient Route To Access Rare Deoxy Amino L-Sugar Building Blocks for the Assembly of Bacterial Glycoconjugates" - Journal of the American Chemical Society 138(14) (2016) 4938-4947
  

  Bacterial glycoproteins and oligosaccharides contain several rare deoxy amino l-sugars which are virtually absent in the human cells. This structural difference between the bacterial and host cell surface glycans can be exploited for the development of carbohydrate based vaccines and target specific drugs. However, the unusual deoxy amino l-sugars present in the bacterial glycoconjugates are not available from natural sources. Thus, procurement of orthogonally protected rare l-sugar building blocks through efficient chemical synthesis is a crucial step toward the synthesis of structurally well-defined and homogeneous complex glycans. Herein, we report a general and expedient methodology to access a variety of unusual deoxy amino l-sugars starting from readily available l-rhamnose and l-fucose via highly regioselective, one-pot double serial and double parallel displacements of the corresponding 2,4-bistriflates using azide and nitrite anions as nucleophiles. Alternatively, regioselective monotriflation at O2, O3, and O4 of l-rhamnose/l-fucose allowed selective inversions at respective positions leading to diverse rare sugars. The orthogonally protected deoxy amino l-sugar building blocks could be stereoselectively assembled to obtain biologically relevant bacterial O-glycans, as exemplified by the first total synthesis of the amino linker-attached, conjugation-ready tetrasaccharide of O-PS of Yersinia enterocolitica O:50 strain 3229 and the trisaccharide of Pseudomonas chlororaphis subsp. aureofaciens strain M71.

  trisaccharide, Pseudomonas, glycoconjugates, vaccines, L-rhamnose, L-fucose, Yersinia enterocolitica, chemical synthesis, O-glycans

  NCBI PubMed ID: 27002789
  Publication DOI: 10.1021/jacs.6b01823
  Journal NLM ID: 7503056
  Publisher: American Chemical Society
  Correspondence: suvarn@chem.iitb.ac.in
  Institutions: Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India
  Methods: 13C NMR, 1H NMR, TLC, GLC, chemical synthesis, chemical methods, MS, glycosylation
  
   
  
  Staphylococcus aureus 5
  CSDB ID 11734 (all data & tools)
• Article ID: 5079
  Weidenmaier C, Lee JC "Structure and Function of Surface Polysaccharides of Staphylococcus aureus" - Book: Staphylococcus aureus (series: Current Topics in Microbiology and Immunology) (2017) Vol. 409, 57-93
  

  The major surface polysaccharides of Staphylococcus aureus include the capsular polysaccharide (CP), cell wall teichoic acid (WTA), and polysaccharide intercellular adhesin/poly-β(1-6)-N-acetylglucosamine (PIA/PNAG). These glycopolymers are important components of the staphylococcal cell envelope, but none of them is essential to S. aureus viability and growth in vitro. The overall biosynthetic pathways of CP, WTA, and PIA/PNAG have been elucidated, and the functions of most of the biosynthetic enzymes have been demonstrated. Because S. aureus CP and WTA (but not PIA/PNAG) utilize a common cell membrane lipid carrier (undecaprenyl-phosphate) that is shared by the peptidoglycan biosynthesis pathway, there is evidence that these processes are highly integrated and temporally regulated. Regulatory elements that control glycopolymer biosynthesis have been described, but the cross talk that orchestrates the biosynthetic pathways of these three polysaccharides remains largely elusive. CP, WTA, and PIA/PNAG each play distinct roles in S. aureus colonization and the pathogenesis of staphylococcal infection. However, they each promote bacterial evasion of the host immune defences, and WTA is being explored as a target for antimicrobial therapeutics. All the three glycopolymers are viable targets for immunotherapy, and each (conjugated to a carrier protein) is under evaluation for inclusion in a multivalent S. aureus vaccine. Future research findings that increase our understanding of these surface polysaccharides, how the bacterial cell regulates their expression, and their biological functions will likely reveal new approaches to controlling this important bacterial pathogen.

  capsular polysaccharide, Staphylococcus aureus, teichoic acid, vaccine, cell wall teichoic acid

  NCBI PubMed ID: 26728067
  Publication DOI: 10.1007/82_2015_5018
  Publisher: Cham: Springer.
  Correspondence: JCLEE@BWH.HARVARD.EDU
  Editors: Bagnoli F, Rappuoli R, Grandi G
  Institutions: Interfaculty Institute for Microbiology and Infection Medicine Tubingen, University of Tubingen and German Center for Infection Research, Tubingen, Germany, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
  
   
  
  Staphylococcus aureus 5
  CSDB ID 12011 (all data & tools)
• Article ID: 5129
  Berti F, De Ricco R, Rappuoli R "Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines" - Molecules 23(6) (2018) 1340
  

  The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial capsular polysaccharide (CPS) antigens, extracted and purified from microbial cultures and obtained with very high purity, show that many of them are decorated by O-acetyl groups. While these groups are often considered important for the structural identity of the polysaccharides, they play a major role in the functional immune response to some vaccines such as meningococcal serogroup A and Salmonella typhi Vi, but do not seem to be important for many others, such as meningococcal serogroups C, W, Y, and type III Group B Streptococcus. This review discusses the O-acetylation status of CPSs and its role in the immunological responses of these antigens.

  O-acetylation, Bacterial polysaccharide, conjugate vaccines, Bacterial Vaccines, carbohydrate antigens

  NCBI PubMed ID: 29865239
  Publication DOI: 10.3390/molecules23061340
  Journal NLM ID: 100964009
  Publisher: Basel, Switzerland: MDPI
  Correspondence: rino.x.rappuoli@gsk.com
  Institutions: External R&D, GSK Vaccines, 53100 Siena, Italy, External R&D, GSK Vaccines, 53100 Siena, Ital
  
   
  
  Staphylococcus aureus 5
  CSDB ID 13051 (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
  
   
  
  Staphylococcus aureus 5
  CSDB ID 12715 (all data & tools)
• Article ID: 5731
  Behera A, Rai D, Kulkarni SS "Total Syntheses of Conjugation-Ready Trisaccharide Repeating Units of Pseudomonas aeruginosa O11 and Staphylococcus aureus Type 5 Capsular Polysaccharide for Vaccine Development" - Journal of the American Chemical Society 142(1) (2020) 456-467
  

  Pseudomonas aeruginosa belongs to the group of three 'critical priority' multi-drug-resistant pathogens listed by WHO and is responsible for severe and often deadly infections such as bloodstream infections and pneumonia. Staphylococcus aureus is also a 'high priority' pathogen which is a major cause of serious nosocomial infections such as bacteremia, sepsis, and endocarditis. Owing to their ability to adapt resistance to almost any antibiotics, vaccines against these pathogens are urgently required. These pathogens express structurally unique and densely functionalized glycans on their surfaces which are absent on the host cells. Such carbohydrate antigens are valuable targets for the development of glycoconjugate vaccines and diagnostics. Here, we report the first total synthesis of the conjugation-ready trisaccharide repeating unit of Pseudomonas aeruginosa O11 via a highly stereoselective and efficient assembly of a rare l-fucosamine- and d-fucosamine-containing 1,2-cis-linked disaccharide motif and its regioselective glycosylation at O3. A systematic study was conducted for the notoriously difficult glycosylation with the most unreactive axial 4-OH of the rare disaccharide, and the successful outcome was utilized to accomplish the total synthesis of an aminopropyl linker-attached trisaccharide repeating unit of Staphylococcus aureus capsular polysaccharide type 5, which is also a potential antigen for immunotherapy and vaccine development. The judicious selection of protecting groups and reaction conditions allowed the stereoselective assembly and selective functional group interconversions to access the structurally complex linker-attached trisaccharide repeating units, which are valuable tools for immunological evaluation and vaccine development. The strategy is useful for the synthesis of other structurally related complex glycans.

  repeating unit, trisaccharide, capsular polysaccharide, Pseudomonas aeruginosa, Staphylococcus aureus, vaccine, chemical synthesis

  NCBI PubMed ID: 31815459
  Publication DOI: 10.1021/jacs.9b11309
  Journal NLM ID: 7503056
  Publisher: American Chemical Society
  Correspondence: Suvarn S. Kulkarni
  Institutions: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
  Methods: 13C NMR, 1H NMR, IR, TLC, chemical synthesis, chemical methods, glycosylation, HR-ESI-MS
  
   
  
  Staphylococcus aureus 5
  CSDB ID 3270 (all data & tools)
• Article ID: 5790
  Khanam A, Tiwari A, Mandal PK "Chiral auxiliaries: Usefullness in stereoselective glycosylation reactions and their synthetic applications" - Carbohydrate Research 495 (2020) 108045
  

  Oligosaccharides play a very important role in biological system and structure-activity relationships that is why it has a lot of application to medicinal chemistry and development of polysaccharide conjugate vaccines. The stereoselective introduction of a glycosidic linkage presents the principal challenge for biological importance oligosaccharide synthesis. The main aim of this review is to described the importance of chiral auxiliary and neibhouring group participation for the stereoselective 1,2-cis glycosidic bonds formation and their application in complex oligosaccharide synthesis.Numerous 1,2-cis-linked oligosaccharides and glyconjugates are naturally found in the compounds of blood group, human milk, antigens of bacterial lipopolysaccharide etc.that predominantly increased it's importance in this field.

  Oligosaccharides, glycosylation, stereoselective, 1, 2-Cis glycosidic bonds, Chiral auxiliary

  NCBI PubMed ID: 32679340
  Publication DOI: 10.1016/j.carres.2020.108045
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: pk.mandal@cdri.res.in
  Institutions: Academy of Scientific and Innovative Research, New Delhi, India, Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow, 226031, India.Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow, 226031, India
  
   
  
  Staphylococcus aureus 5
  CSDB ID 32132 (all data & tools)
• Article ID: 5861
  Visansirikul S, Kolodziej SA, Demchenko AV "Staphylococcus aureus capsular polysaccharides: a structural and synthetic perspective" - Organic and Biomolecular Chemistry 18(5) (2020) 783-798
  

  The S. aureus bacterium is surrounded by capsular polysaccharides. These capsular polysaccharides are important in the pathogenesis of staphylococcal infection. There are 11 serotypes of capsular polysaccharides that have been identified, and a majority of strains express capsular polysaccharides type 5 (CP5) or 8 (CP8). The main focus of this review is to describe recent advances in the area of the chemical synthesis of monosaccharide components of S. aureus CP, oligosaccharide assembly and functionalization. Chemical routes to obtain oligosaccharides derived from CP1, CP5 and CP8 represent a compendium of modern classics of the total synthesis of challenging glycan sequences.

  synthesis, carbohydrates, Oligosaccharides, vaccines

  NCBI PubMed ID: 31922180
  Publication DOI: 10.1039/c9ob02546d
  Journal NLM ID: 101154995
  Publisher: The Royal Society of Chemistry
  Correspondence: demchenkoa@umsl.edu
  Institutions: Department of Chemistry and Biochemistry, University of Missouri - St Louis, One University Boulevard, St Louis, MO 63121, USA, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuddhaya Road, Rajathevee, Bangkok, 10400, Thailand, Bioprocess R&D, Biotherapeutics Pharmaceutical Sciences, Pfizer, Inc., 875 Chesterfield Parkway W, Chesterfield, MO 63017, USA
  
   
  
  Staphylococcus aureus 5 Reynold
  CSDB ID 7632 (all data & tools)
• Article ID: 5868
  Whitfield C, Wear SS, Sande C "Assembly of Bacterial Capsular Polysaccharides and Exopolysaccharides" - Annual Review of Microbiology 74 (2020) 521-543
  

  Polysaccharides are dominant features of most bacterial surfaces and are displayed in different formats. Many bacteria produce abundant long-chain capsular polysaccharides, which can maintain a strong association and form a capsule structure enveloping the cell and/or take the form of exopolysaccharides that are mostly secreted into the immediate environment. These polymers afford the producing bacteria protection from a wide range of physical, chemical, and biological stresses, support biofilms, and play critical roles in interactions between bacteria and their immediate environments. Their biological and physical properties also drive a variety of industrial and biomedical applications. Despite the immense variation in capsular polysaccharide and exopolysaccharide structures, patterns are evident in strategies used for their assembly and export. This review describes recent advances in understanding those strategies, based on a wealth of biochemical investigations of select prototypes, supported by complementary insight from expanding structural biology initiatives. This provides a framework to identify and distinguish new systems emanating from genomic studies

  capsular polysaccharide, exopolysaccharide, extracellular polysaccharide, capsule, glycan biosynthesis, glycan export

  NCBI PubMed ID: 32680453
  Publication DOI: 10.1146/annurev-micro-011420-075607
  Journal NLM ID: 0372370
  Correspondence: cwhitfie@uoguelph.ca
  Institutions: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada
  
   
  
  Staphylococcus aureus 5
  CSDB ID 32232 (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
  
   
  
  Staphylococcus aureus 5
  CSDB ID 20915 (all data & tools)
• Article ID: 6318
  Srtefanetti G, Maclennan CA, Micoli F "Impact and Control of Sugar Size in Glycoconjugate Vaccines" - Molecules 27(19) (2022) 6432
  

  Glycoconjugate vaccines have contributed enormously to reducing and controlling encapsulated bacterial infections for over thirty years. Glycoconjugate vaccines are based on a carbohydrate antigen that is covalently linked to a carrier protein; this is necessary to cause T cell responses for optimal immunogenicity, and to protect young children. Many interdependent parameters affect the immunogenicity of glycoconjugate vaccines, including the size of the saccharide antigen. Here, we examine and discuss the impact of glycan chain length on the efficacy of glycoconjugate vaccines and report the methods employed to size polysaccharide antigens, while highlighting the underlying reaction mechanisms. A better understanding of the impact of key parameters on the immunogenicity of glycoconjugates is critical to developing a new generation of highly effective vaccines.

  glycoconjugates, vaccine, immunogenicity, fragmentation of polysaccharides, sugar length

  NCBI PubMed ID: 36234967
  Publication DOI: 10.3390/molecules27196432
  Journal NLM ID: 100964009
  Publisher: Basel, Switzerland: MDPI
  Correspondence: G. Srtefanetti
  Institutions: Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy, Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation, 500 5th Ave. N, Seattle, WA 98109, USA, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK, The Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK, GSK Vaccines Institute for Global Health, 53100 Siena, Italy
  
   
  
  Staphylococcus aureus 5
  CSDB ID 8827 (all data & tools)

Show legend Show as text

Structure type: polymer chemical repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_240849

• Article ID: 2168
  Moreau M, Richards JC, Fournier JM, Byrd RA, Karakawa WW, Vann WF "Structure of the type 5 capsular polysaccharide of Staphylococcus aureus" - Carbohydrate Research 201(2) (1990) 285-297
  

  The Staphylococcus aureus type 5 capsular polysaccharide is composed of 2-acetamido-2-deoxy-l-fucose (1 part), 2-acetamido-2-deoxy-d-fucose (1 part), and 2-acetamido-2-deoxy-d-mannuronic acid (1 part). On the basis of methylation analysis, optical rotation, high-field one- and two-dimensional 1H- and 13C-n.m.r. experiments, and selective cleavage with 70% aqueous hydrogen fluoride, the polysaccharide was found to be a partially O-acetylated (50%) polymer of the repeating trisaccharide unit, [→4)-3-O-Ac-β-d-ManpNAcA-(1→4)-α-l-FucpNAc-(1→3)-β-d-FucpNAc-(1→]n.

  NCBI PubMed ID: 2224883
  Publication DOI: 10.1016/0008-6215(90)84244-O
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Institutions: Office of Biologics Research and Review, Food and Drug Administration, Bethesda, MD, USA, U.S.A., Division of Biological Sciences, National Research Council of Canada, Ottawa K1A OR6 Canada, Unité du Cholerá et des Vibrions, Institut Pasteur, F-75724 Paris France
  Methods: gel filtration, 13C NMR, 1H NMR, methylation, GLC-MS, GLC, HF treatment
  
   
  
  Staphylococcus aureus 5
  CSDB ID 115941 (all data & tools)

Show legend Show as text

Structure type: polymer biological repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_240847,IEDB_240849

• Article ID: 5791
  Knirel YA, Van Calsteren M "Bacterial exopolysaccharides" - Book: Comprehensive Glycoscience: From Chemistry to Systems Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering (2021) 1-75
  

  Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.

  polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component

  Publication DOI: 10.1016/B978-0-12-819475-1.00005-5
  Publisher: Elsevier
  Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
  Editors: Barchi J, Kamerling H
  Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada
  
   
  
  Staphylococcus aureus 5
  CSDB ID 25086 (all data & tools)