Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Shigella flexneri [ICD11:
XN7Y2 
]
NCBI PubMed ID: 21030536Journal NLM ID: 9104124Publisher: IRL Press at Oxford University Press
Correspondence: theillet
fmp-berlin.de
Institutions: Unite de RMN des Biomolecules, CNRS URA 2185, Institut Pasteur, 25-28 rue du Dr Roux, Paris Cedex 15, France
The O-antigen (O-Ag), the polysaccharide part of the lipopolysaccharide (LPS), is the major target of the serotype-specific protective humoral response elicited upon host infection by Shigella flexneri, the main causal agent of the endemic form of bacillary dysentery. The O-Ag repeat units (RUs) of twelve S. flexneri serotypes share the tetrasaccharide backbone →2)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-α-L-Rhap-(1→3)-β-D-GlcpNAc-(1→, with site selective glucosylation(s) and/or O-acetylation defining the serotypes. To investigate the conformational basis of serotype-specificity, we sampled conformational behaviours during 60 ns of molecular dynamic simulations for oligosaccharides representing three RUs of each one of the O-Ags corresponding to serotypes 1a, 1b, 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, X and Y, respectively. The calculated trajectories were checked by NMR for 1a, 2a, 3a and 5a O-Ags. The simulations predict that in all O-Ags, but 1a and 1b, serotype-specific substitutions of the backbone do not induce any new backbone conformations compared to the linear type O-Ag Y, although they restrain locally the accessible conformational space. Moreover, the influence of any given substituent on the backbone is independent of the eventual presence of other substituents. Finally, only slight differences of conformational behaviour between terminal and inner RUs were observed. These results suggest that the reported serotype-specificity of the protective immune response is not due to recognition of distinct backbone conformations, but to binding of the serotype-defining substituents in the O-Ag context. The gained knowledge is discussed in terms of impact on the development of a broad-serotype coverage vaccine.
O-antigen, Shigella flexneri, vaccine, conformational behaviour, polysaccharide substitutions
Structure type: polymer chemical repeating unit
Location inside paper: p. 110, fig.1
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_125613,IEDB_125614,IEDB_127514,IEDB_130422,IEDB_133752,IEDB_133753,IEDB_133754,IEDB_135813,IEDB_135849,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_141815,IEDB_141816,IEDB_142488,IEDB_143253,IEDB_144998,IEDB_146664,IEDB_151531,IEDB_153213,IEDB_225177,IEDB_885823,IEDB_983931,SB_192
Methods: conformation analysis, MD simulations
3D data: 3D data
Related record ID(s): 26363, 26496, 26497, 26498, 26499, 26500, 26501, 26502, 26503, 26504, 26505, 26507, 26508
NCBI Taxonomy refs (TaxIDs): 623Reference(s) to other database(s): GTC:G36735BW, GlycomeDB:
37319
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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