Taxonomic group: bacteria / Firmicutes, Proteobacteria, Proteobacteria, Proteobacteria, Proteobacteria
(Phylum: Firmicutes, Proteobacteria, Proteobacteria, Proteobacteria, Proteobacteria)
Associated disease: infection due to Staphylococcus aureus [ICD11:
XN6BM 
];
infection due to Escherichia coli [ICD11:
XN6P4 ];
infection due to Yersinia pestis [ICD11:
XN6QS ];
infection due to Bordetella pertussis [ICD11:
XN23B ];
infection due to Acinetobacter baumannii [ICD11:
XN8LS ]
The structure was elucidated in this paperNCBI PubMed ID: 19948836Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: gpier
channing.harvard.edu
Institutions: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, Moscow, Russia, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, Massachusetts, Division of Infectious Diseases, Department of Medicine, University Hospital Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
Vaccines for pathogens usually target strain-specific surface antigens or toxins and rarely is there broad antigenic specificity extending across multiple species. Protective antibodies for bacteria are usually specific for surface or capsular antigens. β-(1→6)-poly-N-acetyl-d-glucosamine (PNAG) is a surface polysaccharide produced by many pathogens, including Staphylococcus aureus, Escherichia coli, Yersinia pestis, Bordetella pertussis, Acinetobacter baumannii and others. Protective antibodies to PNAG are elicited when a deacetylated glycoform (dPNAG, <30% acetates) is used in conjugate vaccines whereas highly acetylated PNAG does not induce such antibodies. Chemical derivation of dPNAG from native PNAG is imprecise, so we synthesized both β-(1→6)-d-glucosamine (GlcNH2) and β-(1→6)-d-N-acetylglucosamine (GlcNAc) oligosaccharides with linkers on the reducing terminus that could be activated to produce sulfhydryl groups for conjugation to bromacetyl groups introduced onto carrier proteins. Synthetic 5- or 9-mer GlcNH2 conjugated to tetanus toxoid (TT) elicited mouse antibodies that mediated opsonic killing of multiple S. aureus strains, while the antibodies that were produced to the 5- or 9-mer GlcNAc-TT did not mediate opsonic killing. Rabbit antibodies to 9GlcNH2-TT bound to PNAG and dPNAG antigens, mediated killing of S. aureus and E. coli, and protected against S. aureus skin abscesses and lethal E. coli peritonitis. Chemical synthesis of a series of oligoglucosamine ligands with defined differences in N-acetylation allowed us to identify a conjugate vaccine formulation that generated protective immune responses to two of the most challenging bacterial pathogens. This vaccine could potentially be used to engender protective immunity to the broad range of pathogens that produce surface PNAG.
vaccines, conjugate, β-Glucans, Escherichia coli Infections, peritonitis, Staphylococcal Skin Infections
Structure type: homopolymer ; n=5,9
Location inside paper: abstract, p.765, fig.1
Aglycon: spacer
Trivial name: PNAG
Compound class: EPS
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_753248
Methods: NMR, ELISA, chemical synthesis, MS, statistical analysis, surface plasmon resonance (SPR)
Biological activity: chemical analysis of the conjugate vaccines, immunologic activities data, animal protection studies
Synthetic data: chemical
Related record ID(s): 25650
NCBI Taxonomy refs (TaxIDs): 1280,
562,
632,
520,
470Reference(s) to other database(s): GTC:G11006VI, GlycomeDB:
11210
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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