Year: 2019
Type: article
Abstract: 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.
Source: PLoS Genetics
Authors: Hong Li, Michael Marceau, Tiandi Yang, Tingting Liao, Xiaoqiong Tang, Renwei Hu, Yan Xie, Hong Tang, Alfred Tay, Ying Shi, Yalin Shen, Tiankuo Yang, Xuenan Pi, Binit Lamichhane, Yong Luo, Aleksandra W. Debowski, Hans-Olof Nilsson, Stuart M. Haslam, Barbara Mulloy, Anne Dell, Keith A. Stubbs, Barry J. Marshall, Mohammed Benghezal
Institutions: The University of Western Australia, Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy, Centre National de la Recherche Scientifique, Inserm, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Center for Infection and Immunity of Lille, Imperial College London, Chengdu University of Technology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,350
Funders: Wellcome Trust, University of Western Australia, National Natural Science Foundation of China, Sichuan University, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, Australian Research Council, National Health and Medical Research Council, West China Hospital, Sichuan University
Awards: G2489160898, Core Support for Collaborative Research in Glycobiology, G331293605, The development of tools to study carbohydrate-processing enzymes implicated in human disease, G5751882405, Using genetic tools to study Helicobacter pylori pathogenesis and persistence, G7899741169, G793818989
OpenAlex ID: W2991459893