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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11: XN6P4

]

NCBI PubMed ID: 17544324
Publication DOI: 10.1016/j.ijmm.2007.04.002
Journal NLM ID: 100898849
Publisher: Jena, Germany: Urban & Fischer Verlag
Correspondence: sml

fz-borstel.de
Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany

Lipopolysaccharide (LPS, endotoxin) elicits an immune reaction which is responsible for many of the harmful effects seen in septic shock patients. The eradication of bacteria by antibiotics is insufficient to resolve the pathology due to the lack of LPS neutralization. LPS-neutralizing antibodies have been described; however, these were specific for the serotype of the infecting bacteria and thus not useful for the treatment of septic shock patients. Structural analyses revealed that the LPS structures of Escherichia coli and Salmonella are structurally conserved in the inner core region. Using whole LPS and a panel of neoglycoconjugates containing purified LPS oligosaccharides, which we have obtained from all E. coli core types (K-12, R1, R2, R3 and R4), Salmonella enterica, and the mutant strain E. coli J-5, we have identified an epitope which is bound with high affinity by the monoclonal antibody WN1 222-5, which has been shown previously shown to be cross-reactive against a large collection of blood,fecal, and urinary isolates of E. coli, S. enterica, some Citrobacter, independently of the serotype [Di Padova, F.E., Brade, H., Barclay, G.R., Poxton, I.R., Liehl, E., Schuetze, E., Kocher, H.P., Ramsay, G., Schreier, M.H., McClelland, D.B., Rietschel, E.T., 1993. A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides. Infect. Immun. 61, 3863-3872]. Importantly, WN1 222-5 was protective in various models of endotoxic shock. The minimal structural element necessary for high-affinity binding consists of R(1)-α-D-Glcp-(1→3)-[L-α-D-Hepp-(1→7)]-L-α-D-Hepp4P-(1→3)-R(2) (R(1), R(2)=additional sugars of LPS) in which the side-chain heptose and the 4-phosphate on the branched heptose are the main determinants of the epitope. Additional sugars of the outer core (R(1)) enhance the affinity, whereas loss of an intact Kdo region and/or lipid A (R(2)) prevent binding. The identification of the epitope provides the structural basis for the rational development of a potential vaccine against E. coli LPS

Lipopolysaccharide, core, antibody, epitope, sepsis, therapy

Structure type: oligomer
Location inside paper: p.327, fig.6, E.coli R1, OS 1
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_130670,IEDB_131186,IEDB_133751,IEDB_135394,IEDB_135818,IEDB_136906,IEDB_137472,IEDB_140088,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_150908,IEDB_151528,IEDB_151531,IEDB_153543,IEDB_190606,IEDB_2189047,IEDB_226811,IEDB_983931,SB_192,SB_7

Methods: chemical analysis, serological methods
Biological activity: serological data
Comments, role: review; structure after alkaline degradation of E. coli LPS

Related record ID(s): 5529
NCBI Taxonomy refs (TaxIDs): 562
Reference(s) to other database(s): GlycomeDB:26680
Show glycosyltransferases

There is only one chemically distinct structure:

N[C@H]1[C@@H](OP(=O)(O)O)O[C@H](CO[C@@H]2O[C@H](CO[C@]3(C(=O)O)C[C@@H](O[C@]4(C(=O)O)C[C@@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O4)[C@@H](O[C@H]4O[C@H]([C@@H](O)CO)[C@@H](OP(=O)(O)O)[C@H](O[C@H]5O[C@H]([C@@H](O)CO[C@H]6O[C@H]([C@@H](O)CO)[C@@H](O)[C@H](O)[C@@H]6O)[C@@H](OP(=O)(O)O)[C@H](O[C@H]6O[C@H](CO)[C@@H](O)[C@H](O[C@H]7O[C@H](CO)[C@@H](O)[C@H](O[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O)[C@H]7O[C@H]7O[C@H](CO)[C@H](O)[C@H](O)[C@H]7O[C@H]7O[C@H](CO)[C@H](O)[C@H](O)[C@H]7O)[C@H]6O)[C@@H]5O)[C@@H]4O)[C@@H]([C@H](O)CO)O3)[C@@H](OP(=O)(O)O)[C@H](O)[C@H]2N)[C@@H](O)[C@@H]1O

SVG MW SMILES 3D mol Ionize