Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: peptic ulcer [ICD11: DA61 , ICD11: XN3DY ]; gastric cancer [ICD11: 2B72.Z ]; infection due to Helicobacter pylori [ICD11: XN3DY ]
 
The structure was elucidated in this paper
NCBI PubMed ID: 28306723
Publication DOI: 10.1371/journal.ppat.1006280
Journal NLM ID: 101238921
Publisher: San Francisco, CA: Public Library of Science
Correspondence: AD <a.dellimperial.ac.uk>; MB <mbenghezalswissvitamin.ch>
Institutions: School of Chemistry and Biochemistry, University of Western Australia, Crawley, Australia, West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China, Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom, Helicobacter pylori Research Laboratory and Ondek Pty Ltd., School of Pathology & Laboratory Medicine, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia, Swiss Vitamin Institute, Route de la Corniche 1, Epalinges, Switzerland

Helicobacter pylori lipopolysaccharide promotes chronic gastric colonisation through O-antigen host mimicry and resistance to mucosal antimicrobial peptides mediated primarily by modifications of the lipid A. The structural organisation of the core and O-antigen domains of H. pylori lipopolysaccharide remains unclear, as the O-antigen attachment site has still to be identified experimentally. Here, structural investigations of lipopolysaccharides purified from two wild-type strains and the O-antigen ligase mutant revealed that the H. pylori core-oligosaccharide domain is a short conserved hexasaccharide (Glc-Gal-DD-Hep-LD-Hep-LD-Hep-KDO) decorated with the O-antigen domain encompassing a conserved trisaccharide (-DD-Hep-Fuc-GlcNAc-) and variable glucan, heptan and Lewis antigens. Furthermore, the putative heptosyltransferase HP1284 was found to be required for the transfer of the third heptose residue to the core-oligosaccharide. Interestingly, mutation of HP1284 did not affect the ligation of the O-antigen and resulted in the attachment of the O-antigen onto an incomplete core-oligosaccharide missing the third heptose and the adjoining Glc-Gal residues. Mutants deficient in either HP1284 or O-antigen ligase displayed a moderate increase in susceptibility to polymyxin B but were unable to colonise the mouse gastric mucosa. Finally, mapping mutagenesis and colonisation data of previous studies onto the redefined organisation of H. pylori lipopolysaccharide revealed that only the conserved motifs were essential for colonisation. In conclusion, H. pylori lipopolysaccharide is missing the canonical inner and outer core organisation. Instead it displays a short core and a longer O-antigen encompassing residues previously assigned as the outer core domain. The redefinition of H. pylori lipopolysaccharide domains warrants future studies to dissect the role of each domain in host-pathogen interactions. Also enzymes involved in the assembly of the conserved core structure, such as HP1284, could be attractive targets for the design of new therapeutic agents for managing persistent H. pylori infection causing peptic ulcers and gastric cancer.

Lipopolysaccharide, O-antigen, core oligosaccharide, Helicobacter pylori, host-pathogen interactions

Structure type: polymer chemical repeating unit ; n=0-6
Location inside paper: fig.1A, fig.1B, fig.1C, O-antigen part of LPS
Aglycon: aXDDmanHepp(1-2) - outer core - inner core - lipid A
Trivial name: Lewis-x
Compound class: O-polysaccharide
Contained glycoepitopes: IEDB_130646,IEDB_130654,IEDB_130655,IEDB_130697,IEDB_135813,IEDB_136044,IEDB_136045,IEDB_136095,IEDB_137340,IEDB_137472,IEDB_137776,IEDB_140108,IEDB_140122,IEDB_141500,IEDB_141794,IEDB_141807,IEDB_142489,IEDB_144556,IEDB_144562,IEDB_145669,IEDB_147455,IEDB_149557,IEDB_150092,IEDB_150939,IEDB_151531,IEDB_152214,IEDB_158550,IEDB_174333,IEDB_190606,IEDB_2151203,IEDB_461720,IEDB_952752,SB_157,SB_165,SB_166,SB_173,SB_187,SB_195,SB_30,SB_7,SB_86,SB_88
 
Methods: 1H NMR, methylation, PCR, SDS-PAGE, DNA techniques, Western blotting, MALDI-TOF MS, methanolysis, genetic methods, permethylation, CE-ESI-MS, SDS-Tricine-PAGE, HF hydrolysis
Comments, role: O-unit of 12169, 12170; in the O-antigen part of previously proposed LPS structures of the 26695 wild-type (A) the degree of polymerization was not indicated.
 
Related record ID(s): 11932, 12169, 12170
NCBI Taxonomy refs (TaxIDs): 85962, 563041
Reference(s) to other database(s): GTC:G83698PM
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