Lipopolysaccharides of Campylobacter jejuni serotype O:19: Structures of O antigen chains from the serostrain and two bacterial isolates from patients with the Guillain-Barre syndrome (original) (raw)

Lipopolysaccharides of Campylobacter jejuni serotype O:19: Structures of core oligosaccharide regions from the serostrain and two bacterial isolates from patients with the Guillain-Barre syndrome

Biochemistry, 1994

An 0 antigenic polysaccharide was liberated from the lipopolysaccharide of high Mr from Campylobacter jejuni serotype 0:19 by acetic acid hydrolysis of the ketosidic linkage to lipid A. The structure of the polysaccharide was established in several one-and two-dimensional lH and 13C N M R experiments, fast atom bombardment mass spectrometry and methylation linkage analysis of the permethylated glycan and its degradation products. It is concluded that the glycan is a derivative of hyaluronic acid in which the 6-D-glucuronic acid residues in the alternating sequence [-4)-p-~-GlcA-( 1+3)-/3-~-GlcNAc-(11" are present as amides of 2-amino-2-deoxyglycerol. Parallel experiments were performed on 0 antigens liberated from lipopolysaccharides of high M r from bacterial isolates that had been obtained from two patients who subsequently developed the Guillain-Barr6 syndrome. Within the limits of structural analysis by N M R spectroscopy and methylation linkage analysis, both these 0 antigens were identical to that from the serostrain.

Structural Characterization of Campylobacter jejuni Lipooligosaccharide Outer Cores Associated with Guillain-Barré and Miller Fisher Syndromes

Infection and Immunity, 2007

Molecular mimicry between lipooligosaccharides (LOS) of Campylobacter jejuni and gangliosides in peripheral nerves plays a crucial role in the pathogenesis of C. jejuni -related Guillain-Barré syndrome (GBS). We have analyzed the LOS outer core structures of 26 C. jejuni strains associated with GBS and its variant, Miller Fisher syndrome (MFS), by capillary electrophoresis coupled with electrospray ionization mass spectrometry. Sixteen out of 22 (73%) GBS-associated and all 4 (100%) MFS-associated strains expressed LOS with ganglioside mimics. GM1a was the most prevalent ganglioside mimic in GBS-associated strains (10/22, 45%), and in eight of these strains, GM1a was found in combination with GD1a mimics. All seven strains isolated from patients with ophthalmoplegia (GBS or MFS) expressed disialylated (GD3 or GD1c) mimics. Three out of 22 GBS-associated strains (14%) did not express sialylated ganglioside mimics because their LOS locus lacked the genes necessary for sialylation. Th...

Lipopolysaccharides from Campylobacter jejuni associated with Guillain-Barre syndrome patients mimic human gangliosides in structure

Infection and …, 1994

Three Campylobacter jejuni, biotype 2, serotype O:41 strains that were isolated from patients who developed Guillain-Barré syndrome (GBS) and one C. jejuni isolate from a patient who developed enteritis only were examined. The aim of the study was to determine the structure of the core oligosaccharide (OS) of the lipopolysaccharide (LPS) of C. jejuni serotype O:41, a serotype rarely associated with the development of GBS, and to determine if the LPS shares similar epitopes with any of the major human gangliosides. Electrophoretic analysis with silver staining or immunoblotting demonstrated that the strains had LPS profiles characteristic of low-molecular-weight LPS. Colorimetric analysis detected N-acetylneuraminic (sialic) acid in the core OSs of all the strains. Thin-layer chromatography with immunostaining showed that antisera raised against the GBS strains reacted with the GM 1 ganglioside, suggesting that C. jejuni serotype O:41 LPSs and the GM 1 ganglioside have similar epitopes. Furthermore, polyclonal anti-GM 1 and anti-asialoGM 1 antibodies cross-reacted with each C. jejuni O:41 LPS tested, suggesting that the serotype O:41 core OS has a GM 1-and asialoGM 1-like structure. LPSs extracted from C. jejuni serostrains O:2, O:3, and O:19 were also used in the study. Cholera toxin (a GM 1 ligand) and peanut agglutinin (a Gal␤1-3GalNAc ligand) recognized all serotype O:41 LPSs and the serostrain O:2 LPS. Immunoadsorption results confirmed GM 1 relatedness. Moreover, the core OS was isolated from a GBS-associated C. jejuni O:41 LPS by gel permeation chromatography. An analysis by gasliquid chromatography (GLC), GLC-mass spectrometry, and nuclear magnetic resonance showed the core OS of one of the C. jejuni O:41 GBS isolates to have a tetrasaccharide structure consistent with GM 1 mimicry.

Lipooligosaccharide of Campylobacter jejuni

Journal of Biological Chemistry, 2011

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 tumorassociated 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 P k 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.

Biological and serological characterization of Campylobacter jejuni lipopolysaccharides with deviating core and lipid A structures

FEMS Immunology & Medical Microbiology, 1995

Lipopoiysaccharides from Campyfobacter jejzmi were tested for their ability to induce toxic lethality in galactosaminesensitized mice, pyrogenicity in rabbits and tumour necrosis factor (TNF) secretion from mouse peritoneal macrophages. Compared with those of Salmonella LPS, lethal toxicity was 50% lower, pyrogenicity was 30-to 50-fold lower, and ability to induce TNF was 100-fold lower. C. jejuni LPS and lipid A exhibited higher phase-transition temperatures than those of Salmonella preparations, and thus the former have lower fluidity at 37" C. This lower fluidity of acyl chains may influence the biological activities of C. jejuni LPS, but acyl chain characteristics and diaminoglucose replacing glucosamine in the hydrophilic lipid A backbone may also influence the supramolecular structure of lipid A, thereby affecting biological activities. Although diaminoglucose is present in the backbone of C. jejuni lipid A, antigenically the latter resembled classical lipid A of the Enterobacteriaceae when tested with anti-lipid A antibodies. Chemical investigations suggested the presence of glucuronic acid in an acid labile linkage in the inner core region, thus producing a structurally unusual region in C. jejuni LPS.

Genetic and biochemical evidence of a Campylobacter jejuni capsular polysaccharide that accounts for Penner serotype specificity: Genetics and biochemistry of C. jejuni LPS biosynthesis

Mol Microbiol, 2002

Campylobacter jejuni, a Gram-negative spiral bacterium, is the most common bacterial cause of acute human gastroenteritis and is increasingly recognized for its association with the serious post-infection neurological complications of the Miller-Fisher and Guillain-Barré syndromes. C. jejuni lipopolysaccharide (LPS) is thought to be involved in the pathogenesis of both uncomplicated infection and more serious sequelae, yet the LPS remains poorly characterized. Current studies on C. jejuni suggest that all strains produce lipooligosaccharide (LOS), with about one-third of strains also producing high-molecular-weight LPS (referred to as O-antigen). In this report, we demonstrate the presence of the high-molecular-weight LPS in all C. jejuni strains tested. Furthermore, we show that this LPS is biochemically and genetically unrelated to LOS and is similar to group II and group III capsular polysaccharides. All tested kpsM, kpsS and kpsC mutants of C. jejuni lost the ability to produce O-antigen. Moreover, this correlated with serotype changes. We demonstrate for the first time that the previously described O-antigen of C. jejuni is a capsular polysaccharide and a common component of the thermostable antigen used for serotyping of C. jejuni.

Genetic and biochemical evidence of a Campylobacter jejuni capsular polysaccharide that accounts for Penner serotype specificity

2002

Campylobacter jejuni, a Gram-negative spiral bacterium, is the most common bacterial cause of acute human gastroenteritis and is increasingly recognized for its association with the serious post-infection neurological complications of the Miller±Fisher and Guillain±Barre  syndromes. C. jejuni lipopolysaccharide (LPS) is thought to be involved in the pathogenesis of both uncomplicated infection and more serious sequelae, yet the LPS remains poorly characterized. Current studies on C. jejuni suggest that all strains produce lipooligosaccharide (LOS), with about one-third of strains also producing highmolecular-weight LPS (referred to as O-antigen). In this report, we demonstrate the presence of the highmolecular-weight LPS in all C. jejuni strains tested. Furthermore, we show that this LPS is biochemically and genetically unrelated to LOS and is similar to group II and group III capsular polysaccharides. All tested kpsM, kpsS and kpsC mutants of C. jejuni lost the ability to produce O-antigen. Moreover, this correlated with serotype changes. We demonstrate for the first time that the previously described Oantigen of C. jejuni is a capsular polysaccharide and a common component of the thermostable antigen used for serotyping of C. jejuni.

Campylobacter infections and Guillain Barré syndrome

Journal of Gastrointestinal Infections

Guillain Barré syndrome (GBS) is a serious disorder of the peripheral nerves preceded by a recognized acute infectious illness. Campylobacter jejuni has been recognized as an important pathogen precipitating GBS and the structure of C. jejuni lipooligosaccharide (LOS) might have a role in the outcome of infection. The development of GBS and Miller Fisher syndrome has been reported to be due to expression of a GM1 like LOS in class A strains and GQ1b like LOS in class B strains of C. jejuni respectively. Virulence of C. jejuni, subtle differences in the interaction between different strains with the host T lymphocyte receptor and MHC class II and host susceptibility may have a role to play in the development of GBS. A humoral immunopathogenic mechanism for GBS has been envisaged as the disease develops 1 to 3 weeks after C. jejuni infection. Antibodies to C. jejuni may remain elevated for several weeks after acute infection. Host susceptibility factors are also important in the pathogenesis of GBS as this disease occurs within families. Association between the occurrence of GBS and a particular HLA type has been envisaged, but studies to prove it are inconclusive. Despite our increasing understanding of the pathophysiology of GBS, the triggering event leading to the disease is still indeed a great puzzle. This review describes the in-depth association of Campylobacter infections with GBS.

Molecular mimicry in Campylobacter jejuni: role of the lipo‐oligosaccharide core oligosaccharide in inducing anti‐ganglioside antibodies

FEMS Immunology …, 2007

Campylobacter jejuni is recognized as the most common identifiable pathogen associated with the development of Guillain-Barré syndrome (GBS), an acute autoimmune-mediated disease affecting the peripheral nervous system. The immune response to ganglioside-like structures in lipo-oligosaccharides (LOSs) of certain C. jejuni strains is thought to cross-react with human nerve gangliosides and induce GBS. To study the involvement of LOSs in the pathogenesis of Campylobacter-induced GBS, we created truncated LOS molecules by inactivating the waaF gene in a GBS-associated isolate of C. jejuni. Gas Chromatography-MS analysis of the waaF mutant LOSs revealed a marked reduction in sugar content, including sialic acid and galactose. GM1 and GD1a-like mimicry was not detected in the waaF mutant by Western blot analysis with cholera toxin B and anti-GD1a antibodies. Mice immunized with the waaF mutant failed to develop anti-GM1 or anti-GD1a antibodies. The waaF mutant also showed reduced adherence to and invasion of INT-407 cells. The results indicate that the LOS of C. jejuni HB93-13 is essential for adherence and invasion as well as for anti-ganglioside antibody induction.