Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: infection due to Citrobacter freundii [ICD11:
XN0M3 
];
infection due to Salmonella typhi [ICD11:
XN4AM ]
NCBI PubMed ID: 31160100Publication DOI: 10.1016/j.vaccine.2019.05.050Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: B. Bolgiano <Barbara.Bolgiano
nibsc.org>
Institutions: Division of Bacteriology, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK, Department of Computer Science, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa, Laboratory of Molecular Structure, Analytical and Biological Sciences, NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK, Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch, 7701 Cape Town, South Africa
In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG. This study also confirms that human anti-Vi sera binds to completely de-O-acetylated Vi. Molecular dynamics simulations provide conformational rationales for the known effect of de-O-acetylation both on the viscosity and antigenicity of the Vi, demonstrating that de-O-acetylation has a very marked effect on the conformation and dynamic behavior of the Vi, changing the capsular polysaccharide from a rigid helix into a more flexible coil, as well as enhancing the strong interaction of the polysaccharide with sodium ions. Partial de-O-acetylation of Vi revealed hidden epitopes that were recognized by human and sheep anti-Vi PS immune sera. These findings have significance for the manufacture and evaluation of Vi vaccines.
molecular modelling, structure, nuclear magnetic resonance, vaccine, bacteriology, glycoconjugate, Enteric, Vi polysaccharide
Structure type: homopolymer
Location inside paper: fig.1
Trivial name: Vi-antigen, Vi antigen, Vi polysaccharide, Vi-antigen (glycotope)
Compound class: CPS
Contained glycoepitopes: IEDB_144984,IEDB_164179,IEDB_164180,IEDB_164181
Methods: 13C NMR, 1H NMR, NMR-2D, ELISA, conformation analysis, de-O-acetylation, serological methods, HPAEC-PAD, molecular modeling, antibody binding, MD simulation, CHARMM computations
3D data: molecular modeling
NCBI Taxonomy refs (TaxIDs): 546,
90370Reference(s) to other database(s): GTC:G67538LH
Show glycosyltransferases
There is only one chemically distinct structure:
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