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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: diarrhea [ICD11: ME05.1

, ICD11: SA55

]; dysentery [ICD11: SA56

]; infection due to Shigella sonnei [ICD11: XN9M9

]

NCBI PubMed ID: 20542498
Publication DOI: 10.1016/j.carres.2010.05.006
Journal NLM ID: 0043535
Publisher: Elsevier
Correspondence: kielbj

mail.nih.gov
Institutions: The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, USA

There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of a Shigella vaccines is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates. This finding is now extended to the O-SPC of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1. The structures of O-SPC, containing core plus 1-4 O-SP repeat units (RUs), were analyzed by NMR and mass spectroscopy. The first RUs attached to the cores of S. flexneri 2a and 6 LPS were different from the following RUs in their O-acetylation and/or glucosylation. Conjugates of core plus more than 1 RU were necessary to induce LPS antibodies in mice. The resulting antibody levels were comparable to those induced by the full length O-SP conjugates. In S. dysenteriae type 1, the first RU was identical to the following RUs, with the exception that the GlcNAc was bound to the core in the β-configuration, while in all other RUs the GlcNAc was present in the α-configuration. In spite of this difference, conjugates of S. dysenteriae type 1 core with 1, 2, or 3 RUs induced LPS antibodies in mice with levels statistically higher than those of the full size O-SP conjugates. O-SPC conjugates are easy to prepare, characterize, and standardize, and their clinical evaluation is planned.

LPS, Shigella, vaccine, conjugate

Structure type: oligomer
Location inside paper: p.1603, fig.2
Trivial name: core type R4
Compound class: core oligosaccharide with O-unit
Contained glycoepitopes: IEDB_130650,IEDB_130670,IEDB_131186,IEDB_133751,IEDB_135818,IEDB_136906,IEDB_137472,IEDB_140088,IEDB_141794,IEDB_141807,IEDB_142345,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_153543,IEDB_190606,IEDB_2189047,IEDB_226811,IEDB_983931,SB_192,SB_7

Methods: 13C NMR, 1H NMR, methylation, SDS-PAGE, sugar analysis, MALDI-TOF MS, NMR-1D, serological methods, statistical analysis, immunization, conjugation
Biological activity: structure and immunogenicity of the core and O-SPC

Related record ID(s): 25317, 25727, 25728
NCBI Taxonomy refs (TaxIDs): 624
Reference(s) to other database(s): GTC:G15485IU, GlycomeDB:37883
Show glycosyltransferases

There are 2 chemically distinct structures. Please, select:

CC(=O)N[C@H]1[C@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3[C@H](O)[C@@H](CO)O[C@H](O[C@H]4[C@H](O)[C@@H](CO)O[C@H](O[C@@H]5[C@H](O)[C@@H](O[C@@H]6[C@H](O)[C@@H](O[C@@H]7[C@H](O)CC(O)(C(=O)O)O[C@@H]7[C@H](O)CO)O[C@H]([C@@H](O)CO)[C@H]6OP(=O)(O)O)O[C@H]([C@@H](O)CO[C@H]6O[C@H]([C@@H](O)CO[C@H]7O[C@H](CO)[C@@H](O)[C@H](O)[C@H]7N)[C@@H](O)[C@H](O)[C@@H]6O)[C@H]5OP(=O)(O)O)[C@@H]4O)[C@@H]3O[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)O[C@H](CO)[C@H]2O)O[C@H](C)[C@H](N)[C@@H]1O[C@@H]1O[C@@H](C(=O)O)[C@H](O)[C@H](O)[C@H]1NC(C)=O

SVG MW SMILES 3D mol Ionize