Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori

Abstract

This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium.

The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains

“…pylori LPS assembly have been identified [13]. Of particular interest is the heptosyltransferase responsible for the transfer of Hep III to which the conserved Trio motif is attached ( Fig 1A ).…”

“…A targeted approach to identify the Hep III transferase of the core LPS was based on the identification of highly conserved putative glycosyltranferases in the H . pylori genome [13]. The putative protein sequence of HP1284 in strain G27 was found to share 36% identity to LPS Hep III transferase WaaQ from Haemophilus influenza 86-028NP.…”

“…The lipid A and Lewis antigens of H . pylori LPS have been well-characterised in terms of biosynthesis, structure and function [13]. However additional work is needed in regard to the characterization of the core-oligosaccharide domain.…”

“…However additional work is needed in regard to the characterization of the core-oligosaccharide domain. Similar to other Gram-negative bacteria [8], the core-oligosaccharide domain of 26695 is conceptually divided into two parts, the inner core and outer core [13]. The inner core is built as a conserved hexasaccharide (Glc-Gal-DD-Hep-LD-Hep-LD-Hep-KDO) and the first two LD-Hep residues (designated as Hep I and Hep II) are added sequentially by heptosyltransferases HP0279 and HP1191 [18].…”

“…pylori 26695 LPS was initially postulated to contain a DD-heptan with the first DD-Hep residue connecting a side-branched α-1,6-glucan [6,16,17,19–22], but a recent reinvestigation into the structure of 26695 LPS revised the outer core as being a linear arrangement of DD-heptan and α-1,6-glucan linked to the inner core through a trisaccharide (GlcNAc-Fuc-DD-Hep) termed as Trio [15] ( Fig 1A ). Furthermore, the attachment site of the O-antigen to the core-oligosaccharide has not been identified [13,15], and therefore the precise assignment of the O-antigen and core-oligosaccharide domains remains unclear.…”