The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains

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Title: The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains
Authors: Li, H
Yang, T
Liao, T
Debowski, AW
Nilsson, H-O
Fulurija, A
Haslam, SM
Mulloy, B
Dell, A
Stubbs, KA
Marshall, BJ
Benghezal, M
Item Type: Journal Article
Abstract: 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.
Issue Date: 17-Mar-2017
Date of Acceptance: 8-Mar-2017
ISSN: 1553-7366
Publisher: Public Library of Science
Journal / Book Title: PLOS Pathogens
Volume: 13
Issue: 3
Copyright Statement: © 2017 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Funder's Grant Number: BB/K016164/1
Keywords: Science & Technology
Life Sciences & Biomedicine
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN e1006280
Appears in Collections:Faculty of Natural Sciences

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