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

]

NCBI PubMed ID: 23219811
Publication DOI: 10.1016/j.micpath.2012.11.011
Journal NLM ID: 8606191
Publisher: Academic Press
Correspondence: I. Moriyon <imoriyon

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Institutions: Institute for Tropical Health and Departamento de Microbiologia y Parasitologia, Universidad de Navarra, Pamplona, Spain, Centre d’Immunologie de Marseille-Luminy, Université Aix-Marseille, Faculté de Sciences de Luminy, INSERM U631, CNRS UMR6102, Marseille, France, Instituto de Agrobiotecnología CSIC-UPNA-Gobierno de Navarra, Pamplona, Spain

The gram-negative bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a world wide-distributed zoonotic disease that represents a serious problem for animal and human health. There is no human-to-human contagion and, since there is no human vaccine, animal vaccination is essential to control brucellosis. However, current vaccines (all developed empirically) do not provide 100% protection and are infectious in humans. Attempts to generate new vaccines by obtaining mutants lacking the lipopolysaccharide O-polysaccharide, in purine metabolism or in Brucella type IV secretion system have not been successful. Here we propose a new approach to develop brucellosis vaccines based on the concept that Brucella surface molecules evade efficient detection by innate immunity, thus delaying protective Th1 responses and opening a time window to reach sheltered intracellular compartments. We showed recently that a branch of the core oligosaccharide section of Brucella lipopolysaccharide hampers recognition by TLR4-MD2. Mutation of glycosyltransferase WadC, involved in the synthesis of this branch, results in a lipopolysaccharide that, while keeping the O-polysaccharide essential for optimal protection, shows a truncated core, is more efficiently recognized by MD2 and triggers an increased cytokine response. In keeping with this, the wadC mutant is attenuated in dendritic cells and mice. In the mouse model of brucellosis vaccines, the Brucella abortus wadC mutant conferred protection similar to that provided by S19, the best cattle vaccine available. The properties of the wadC mutant provide the proof of concept for this new approach and open the way for more effective brucellosis vaccines.

Lipopolysaccharide, vaccines, immunity, Brucella, brucellosis, attenuation

Structure type: oligomer
Location inside paper: p.31, fig.1
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_130670,IEDB_140088,IEDB_150901,IEDB_2189047,IEDB_226811

Methods: serological methods, genetic methods

Related record ID(s): 29459
NCBI Taxonomy refs (TaxIDs): 562
Reference(s) to other database(s): GTC:G64782QP
Show glycosyltransferases

There is only one chemically distinct structure:

O=C(O)[C@@]1(O)C[C@@H](O[C@]2(C(=O)O)C[C@@H](O[C@]3(C(=O)O)C[C@@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O3)[C@@H](O)[C@@H]([C@H](O)CO)O2)[C@@H](O[C@H]2O[C@H]([C@@H](O)CO)[C@@H](OP(=O)(O)O)[C@H](O[C@H]3O[C@H]([C@@H](O)CO[C@H]4O[C@H]([C@@H](O)CO)[C@@H](O)[C@H](O)[C@@H]4O)[C@@H](OP(=O)(O)O)[C@H](O)[C@@H]3O)[C@@H]2O)[C@@H]([C@H](O)CO)O1

SVG MW SMILES 3D mol Ionize