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Found 2 structures.
Displayed structures from 1 to 2
| -4)-b-D-ManpNAcA-(1-4)-a-L-FucpNAc3Ac-(1-3)-b-D-FucpNAc-(1- | Show graphically |
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Structure type: polymer chemical repeating unit
Trivial name: CP5
Compound class: CPS, EPS, O-polysaccharide
Contained glycoepitopes: IEDB_240847,IEDB_240849
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: 15040941gene, capsular, polysaccharide, capsular polysaccharide, type, O-acetylation, identification, Staphylococcus, Staphylococcus aureus
Journal NLM ID: 8712028Antibodies 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: 16087046Glycoconjugate 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: 15797125The 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: 2224883Capsules 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, type, mutant, region, insertion, plasmid, capsule, Staphylococcus, Staphylococcus aureus, fragment, Serotypes, site, clone, PDF, capsules, selection, polymorphism
NCBI PubMed ID: 805001Structural 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: 17009947The 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: 26728067Bacterial 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: 27002789The 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: 26728067The 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: 29865239Cell 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: 29547971Pseudomonas 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, Pseudomonas aeruginosa, capsular polysaccharide, Staphylococcus aureus, vaccine, chemical synthesis
NCBI PubMed ID: 31815459Oligosaccharides 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: 32679340The 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: 31922180Polysaccharides 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: 32680453Antimicrobial 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: 35608633Glycoconjugate 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| -4)-b-D-ManpNAcA-(1-4)-a-L-FucpNAc3Ac-(1-3)-b-D-FucpNAc-(1- | Show graphically |
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Structure type: polymer biological repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_240847,IEDB_240849
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| New query | Export IDs | Home | Help |
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