机构：[1]West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China,[2]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,[3]Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom,[4]School of Chemistry and Biochemistry, University of Western Australia, Crawley, Australia,[5]Swiss Vitamin Institute, Route de la Corniche 1, Epalinges, Switzerland[6]The Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
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.
基金：
This work was supported by a Biotechnology and Biological Sciences Research Council grant (BB/K016164/1, Core Support for Collaborative Research to AD and SMH), and by a Wellcome Trust Senior Investigator Award to AD. This work was supported by an Early Career Research Fellowship from the National Health and Medical Research Council (NHMRC) (APP1073250), ECR Fellowship Support Grant from the University of Western Australia, and an Ada Bartholomew Medical Research Trust Grant to AWD. An ARC Future Fellowship (FT100100291) supported KAS. A grant from West China Hospital, Sichuan University to HL entitled ?1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University? (ZY2016201). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|1 区生物
小类|1 区微生物学1 区寄生虫学1 区病毒学
最新[2023]版：
大类|1 区医学
小类|1 区微生物学1 区寄生虫学1 区病毒学
第一作者：
第一作者机构：[1]West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China,[2]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,
共同第一作者：
通讯作者：
通讯机构：[2]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,[3]Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom,[5]Swiss Vitamin Institute, Route de la Corniche 1, Epalinges, Switzerland
推荐引用方式(GB/T 7714)：
Hong Li,Tiandi Yang,Tingting Liao,et al.The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains.[J].PLoS pathogens.2017,13(3):e1006280.doi:10.1371/journal.ppat.1006280.
APA：
Hong Li,Tiandi Yang,Tingting Liao,Aleksandra W. Debowski,Hans-Olof Nilsson...&Mohammed Benghezal.(2017).The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains..PLoS pathogens,13,(3)
MLA：
Hong Li,et al."The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains.".PLoS pathogens 13..3(2017):e1006280
生物