East-Asian Helicobacter pylori strains synthesize heptan-deficient lipopolysaccharide

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.

Metabolic inhibitors of bacterial glycan biosynthesis

“…S2 †) by an asyet uncharacterized mechanism, yet has no effect on lipopolysaccharide biosynthesis. 66 Small molecule-induced functional defects appeared even more striking than those induced via genetic interruption. Fitness appeared to be most impaired in H. pylori treated with BnBac (1), F-DAT (5) and BnFucNAc (3) (Fig.…”

Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori

“…The HP0102 protein sequence contains several motifs of the glycosyltransferase family 2 (GT-2; www.kegg.jp , http://pfam.sanger.ac.uk/ , http://www.cazy.org/ ), suggesting HP0102 is involved in LPS biosynthesis. While at the time of this study, the precise function of HP0102 was unknown, it was recently described to act as a fucosyltransferase involved in O-chain biosynthesis in H. pylori strain G27 10 . In line with the study by Li and colleagues 10 , we also observed that H. pylori X47-2AL ∆ hp0102 deletion mutants have only rough-form LPS, i.e.…”

“…This long O-antigen comprises a trisaccharide (Trio), a glucan, a DD-heptan, and terminal Lewis antigens. Despite its important roles in immune evasion and persistence, a complete picture of the LPS biosynthesis pathway in H. pylori is only being revealed stepwise 4 , 9 , 10 . This might be due to the dispersed genomic locations of LPS genes throughout the H. pylori genome.…”

Riboregulation in the Major Gastric Pathogen Helicobacter pylori

“…This operon encodes the TlpB chemotaxis receptor and the HP0102 protein that was shown to function as a glycosyltransferase involved in lipopolysaccharide (LPS) O-chain biosynthesis (Pernitzsch et al, 2021). The precise fucosyltransferase activity of HP0102 was shown (Li et al, 2019). The sRNA designated RepG (REgulator of Polymeric G-repeats) is highly conserved in H. pylori.…”