Li H, Marceau M, Liao T, Tang X, Hu R, Xie Y, Tang H, Tay A, Shi Y, Shen Y, Yang T, Pi X, Lamichhane B, Luo Y, Debowski AW, Nilsson HO, Haslam SM, Mulloy B, Dell A, Stubbs KA, Marshall BJ, Benghezal M East-Asian Helicobacter pylori strains synthesize heptan-deficient lipopolysaccharide PLoS Genetics15(11) (2019)
e1008497
The structure was elucidated in this paper NCBI PubMed ID:31747390 Publication DOI:10.1371/journal.pgen.1008497 Journal NLM ID:101239074 Publisher: San Francisco, CA: Public Library of Science Correspondence: htang6198hotmail.com; mbenghezalgmail.com Institutions: Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom, 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, Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France, Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, China, Key Laboratory of Geoscience Spatial Information Technology, Ministry of Land and Resources of the P.R.China, Chengdu University of Technology, School of Molecular Sciences, University of Western Australia, Crawley, Australia, Ondek Pty Ltd, Rushcutters Bay, New South Wales, Australia
The lipopolysaccharide O-antigen structure expressed by the European Helicobacter pylori model strain G27 encompasses a trisaccharide, an intervening glucan-heptan and distal Lewis antigens that promote immune escape. However, several gaps still remain in the corresponding biosynthetic pathway. Here, systematic mutagenesis of glycosyltransferase genes in G27 combined with lipopolysaccharide structural analysis, uncovered HP0102 as the trisaccharide fucosyltransferase, HP1283 as the heptan transferase, and HP1578 as the GlcNAc transferase that initiates the synthesis of Lewis antigens onto the heptan motif. Comparative genomic analysis of G27 lipopolysaccharide biosynthetic genes in strains of different ethnic origin revealed that East-Asian strains lack the HP1283/HP1578 genes but contain an additional copy of HP1105 and JHP0562. Further correlation of different lipopolysaccharide structures with corresponding gene contents led us to propose that the second copy of HP1105 and the JHP0562 may function as the GlcNAc and Gal transferase, respectively, to initiate synthesis of the Lewis antigen onto the Glc-Trio-Core in East-Asian strains lacking the HP1283/HP1578 genes. In view of the high gastric cancer rate in East Asia, the absence of the HP1283/HP1578 genes in East-Asian H. pylori strains warrants future studies addressing the role of the lipopolysaccharide heptan in pathogenesis.
Methods: NMR, Smith degradation, MS/MS, MALDI-TOF MS, methanolysis, genetic methods, permethylation, bioinformatic analysis, mutation analysis, MALDI-TOF/TOF MS, HF hydrolysis, genome analysis Comments, role: LPS structure in G27ΔHPG27_1230 mutant strain is similar to that of H. pylori G27 wild strain.
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]; infection due to Helicobacter pylori [ICD11: XN3DY 
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