Imperial College London
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ProfessorStuartHaslam

Faculty of Natural Sciences, Department of Life Sciences

Professor in Structural Glycobiology
 
 
 
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Contact

 

+44 (0)20 7594 5222s.haslam

 
 
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Location

 

101ASir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Li:2017:10.1371/journal.ppat.1006280,
author = {Li, H and Yang, T and Liao, T and Debowski, AW and Nilsson, H-O and Fulurija, A and Haslam, SM and Mulloy, B and Dell, A and Stubbs, KA and Marshall, BJ and Benghezal, M},
doi = {10.1371/journal.ppat.1006280},
journal = {PLOS Pathogens},
title = {The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains},
url = {http://dx.doi.org/10.1371/journal.ppat.1006280},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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, s
AU  - Li,H
AU  - Yang,T
AU  - Liao,T
AU  - Debowski,AW
AU  - Nilsson,H-O
AU  - Fulurija,A
AU  - Haslam,SM
AU  - Mulloy,B
AU  - Dell,A
AU  - Stubbs,KA
AU  - Marshall,BJ
AU  - Benghezal,M
DO  - 10.1371/journal.ppat.1006280
PY  - 2017///
SN  - 1553-7366
TI  - The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains
T2  - PLOS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1006280
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000398120300021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/49004
VL  - 13
ER  -
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