Lipooligosaccharide of Campylobacter jejuni: SIMILARITY WITH MULTIPLE TYPES OF MAMMALIAN GLYCANS BEYOND GANGLIOSIDES

R Scott Houliston,Evgeny Vinogradov,Monika Dzieciatkowska,Jianjun Li,Frank St Michael,Marie-France Karwaski,Denis Brochu,Harold C Jarrell,Craig T Parker,Nobuhiro Yuki,Robert E Mandrell,Michel Gilbert

doi:10.1074/jbc.m110.181750

Abstract

Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering Guillain-Barré syndrome. We now confirm that this pathogen is capable of synthesizing a much broader spectrum of host glycolipid/glycoprotein mimics within its LOS. P blood group and paragloboside (lacto-N-neotetraose) antigen mimicry is exhibited by RM1221, a strain isolated from a poultry source. RM1503, a gastroenteritis-associated strain, expresses lacto-N-biose and sialyl-Lewis c units, the latter known as the pancreatic tumor-associated antigen, DU-PAN-2 (or LSTa). C. jejuni GC149, a Guillain-Barré syndrome-associated strain, expresses an unusual sialic acid-containing hybrid oligosaccharide with similarity to both ganglio and Pk antigens and can, through phase variation of its LOS biosynthesis genes, display GT1a or GD3 ganglioside mimics. We show that the sialyltransferase CstII and the galactosyltransferase CgtD are involved in the synthesis of multiple mimic types, with LOS structural diversity achieved through evolving allelic substrate specificity.

Highlights

Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering GuillainBarresyndrome
C. jejuni RM1221 LOS Displays Paragloboside and P Blood Group Antigen Mimics—MS analysis of de-O-acylated LOS from RM1221 in negative ion mode (Fig. 3A and supplemental Table S1) showed related doubly, triply, and quadruply charged ions at m/z 1690.5, 1126.5, and 844.5, respectively, which correspond to a species with a mass of ϳ3382.3 Da
C. jejuni RM1503 LOS Displays a Type I Sialyl-Lewis c Mimic— Analysis of intact LOS from RM1503 by MS in the negative ion mode shows the presence of related triply and quadruply charged ions at m/z 1297.2 and 972.7, respectively, which correspond to a species with a mass of ϳ3894.2 Da (Fig. 5A and supplemental Table S3)

Summary

Introduction

Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering GuillainBarresyndrome. C. jejuni GC149, a Guillain-Barresyndrome-associated strain, expresses an unusual sialic acid-containing hybrid oligosaccharide with similarity to both ganglio and Pk antigens and can, through phase variation of its LOS biosynthesis genes, display GT1a or GD3 ganglioside mimics. Seminal investigations by Yuki et al [1] and Aspinall et al [2] established that certain strains of Campylobacter jejuni isolated from patients with Guillain-Barresyndrome (GBS) express lipooligosaccharide (LOS)-bound ganglioside mimics. All strains carry several common essential genes that direct the synthesis of the inner core and lipid A, each locus class is defined by a unique genetic composition and arrangement. The LOS loci in C. jejuni, as a group, are of a mosaic nature with varying levels of similarity

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