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East-Asian Helicobacter pylori Strains Synthesize Heptan-deficient Lipopolysaccharide


Autoři: Hong Li aff001;  Michael Marceau aff003;  Tiandi Yang aff004;  Tingting Liao aff002;  Xiaoqiong Tang aff001;  Renwei Hu aff005;  Yan Xie aff005;  Hong Tang aff001;  Alfred Tay aff002;  Ying Shi aff001;  Yalin Shen aff001;  Tiankuo Yang aff001;  Xuenan Pi aff006;  Binit Lamichhane aff002;  Yong Luo aff007;  Aleksandra W. Debowski aff002;  Hans-Olof Nilsson aff002;  Stuart M. Haslam aff004;  Barbara Mulloy aff004;  Anne Dell aff004;  Keith A. Stubbs aff008;  Barry J. Marshall aff002;  Mohammed Benghezal aff001
Působiště autorů: 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 aff001;  Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia aff002;  Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Center for Infection and Immunity of Lille, Lille, France aff003;  Department of Life Sciences, Imperial College London, South Kensington Campus, London, United Kingdom aff004;  Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China aff005;  Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, China aff006;  Key Laboratory of Geoscience Spatial Information Technology, Ministry of Land and Resources of the P.R.China, Chengdu University of Technology aff007;  School of Molecular Sciences, University of Western Australia, Crawley, Australia aff008;  Ondek Pty Ltd, Rushcutters Bay, New South Wales, Australia aff009
Vyšlo v časopise: East-Asian Helicobacter pylori Strains Synthesize Heptan-deficient Lipopolysaccharide. PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008497
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008497

Souhrn

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.

Klíčová slova:

Antigens – Biosynthesis – Comparative genomics – Endotoxins – Glucans – Helicobacter pylori – Transferases – Glycosyltransferases


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Genetika Reprodukční medicína

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