East-Asian Helicobacter pylori strains synthesize heptan-deficient lipopolysaccharide

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 DellKeith A. Stubbs, Barry J. Marshall, Mohammed Benghezal

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article numbere1008497
JournalPLoS Genetics
Volume15
Issue number11
DOIs
Publication statusPublished - 1 Jan 2019

    Fingerprint

Cite this

Li, H., Marceau, M., Yang, T., Liao, T., Tang, X., Hu, R., ... Benghezal, M. (2019). East-Asian Helicobacter pylori strains synthesize heptan-deficient lipopolysaccharide. PLoS Genetics, 15(11), [e1008497]. https://doi.org/10.1371/journal.pgen.1008497