Campylobacter jejuni-mediated Guillain-Barre Syndrome, an overview of the molecular mimicry and vaccine development approaches (original) (raw)
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Guillain-Barré Syndrome Induced by Campylobacter jejuni
British Microbiology Research Journal, 2015
Purpose of Review: Guillain-Barré syndrome (GBS) is a neurologic disease that produces ascending paralysis that affects people all over the world. Several infectious agents have been associated with GBS and many reports suggest that infection with Campylobacter jejuni, a common enteric pathogen, may cause GBS by triggering demyelination of peripheral nerves. This review provides an update on the C. jejuni infections engaged in the developing of GBS. Summary and Results: Guillain-Barré syndrome is the most common cause of acute neuromuscular paralysis, yet its cause and pathogenesis are unknown. In approximately two thirds of patients, neuropathic symptoms follow an infection-often a mild, undiagnosed respiratory or gastrointestinal illness. The organism that has most frequently been described in association with GBS is C. jejuni, a gram-negative rod that is now the most common cause of bacterial gastroenteritis in developed countries. Although there has been a plethora of case reports and studies documenting the association, the specific clinical and epidemiologic features are not well Review Article Honarmand and Moghadam; BMRJ, 6(2): 71-83, 2015; Article no.BMRJ.2015.060 72 known. In addition, there is controversy about whether those with preceding C. jejuni infection have a more severe form of the GBS. C. jejuni can cause the disease by a mechanism called molecular mimicry. C. jejuni contains ganglioside-like epitopes in the lipopolysaccharide (LPS) moiety that elicit autoantibodies which can react with peripheral nerve targets. It seems that heterogeneity in the LPS structure determines the specificity of the antiglycolipid response and thereby the clinical features in patients with a post-campylobacter infection neuropathy.
Guillain-Barré Syndrome and Campylobacter jejuni Infection: A Review
Delta Medical College Journal, 2014
Guillain-Barre´ syndrome (GBS), a neurologic disease that produces ascending paralysis, affects people all over the world. Acute infectious illness precedes 50%-75% of the GBS cases. Although many infectious agents have been associated with GBS, the strongest documented association is with Campylobacter infection. The first line of evidence supporting Campylobacter infection as a trigger of GBS is anecdotal reports. The second line of evidence is serological surveys, which have demonstrated that sera from GBS patients contain anti Campylobacter jejuni antibodies, consistent with recent infection. Finally, culture studies have proven that a high proportion of GBS patients have C. jejuni in their stools at the time of onset of neurological symptoms. One of every 1058 Campylobacter infections results in GBS. Sialic acid containing lipooligosaccharides (LOS) biosynthesis gene locus are associated with GBS and the expression of ganglioside mimicking structures. GM 1a was the most prevalent ganglioside mimic in GBS associated strains. Molecular mimicry between C. jejuni LOS and gangliosides in human peripheral nerves, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh, like worldwide.
Journal of Clinical Investigation, 2004
Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barré syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies. Nonstandard abbreviations used: Cm r , chloramphenicol resistance; cst-II, campylobacter sialic acid transferase-II; GBS, Guillain-Barré syndrome; LOS, lipo-oligosaccharides; MFS, Miller Fisher syndrome; orf, open reading frame.
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 Gal1-3GalNAc 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.
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.
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.
PLoS ONE, 2012
Background: Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh. Methodology: Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzymelinked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.
Infection and Immunity, 2002
ABSTRACTGanglioside mimicry in the lipopolysaccharide (LPS) fraction ofCampylobacter jejuniisolated from Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) patients was compared with isolates from patients with an uncomplicated enteritis. The antibody response toC. jejuniLPS and gangliosides in neuropathy patients and controls was compared as well. LPS from GBS and MFS-associated isolates more frequently contained ganglioside-like epitopes compared to control isolates. Almost all neuropathy patients showed a strong antibody response against LPS and multiple gangliosides in contrast to enteritis patients. Isolates from GBS patients more frequently had a GM1-like epitope than isolates from MFS patients. GQ1b-like epitopes were present in all MFS-associated isolates and was associated with anti-GQ1b antibody reactivity and the presence of oculomotor symptoms. These results demonstrate that the expression of ganglioside mimics is a risk factor for the development of post-Ca...
European Journal of Clinical Microbiology & Infectious Diseases, 2012
Guillain-Barré syndrome (GBS) is a postinfectious disease in which the human peripheral nervous system is affected after infection by specific pathogenic bacteria, including Campylobacter jejuni. GBS is suggested to be provoked by molecular mimicry between sialylated lipooligosaccharide (LOS) structures on the cell envelope of these bacteria and ganglioside epitopes on the human peripheral nerves, resulting in autoimmune-driven nerve destruction. Earlier, the C. jejuni sialyltransferase (Cst-II) was found to be linked to GBS and demonstrated to be involved in the biosynthesis of the ganglioside-like LOS structures. Apart from a role in pathogenicity, we report here that Cst-II-generated ganglioside-like LOS structures confer efficient bacteriophage resistance in C. jejuni. By bioinformatic analysis, it is revealed that the presence of sialyltransferases in C. jejuni and other potential GBS-related pathogens correlated significantly with the apparent degeneration of an alternative anti-virus system: type II Clusters of Regularly Interspaced Short Palindromic Repeat and associated genes (CRISPR-Cas). Molecular analysis of the C. jejuni CRISPR-Cas system confirmed the bioinformatic investigation. CRISPR degeneration and mutations in the cas genes cas2, cas1 and csn1 were found to correlate with Cst-II Electronic supplementary material The online version of this article