Campylobacter jejuni and the Guillain-Barré Syndrome: the role of bacterial genetic polymorphisms
Campylobacter jejuni en het Guillain-Barré syndroom: de rol van bacteriële genetische polymorfismen
The main aim of the research described in this thesis is to identify genetic markers for GBS in C. jejuni. Many studies have provided evidence for the hypothesis that molecular mimicry between Campylobacter LOS and gangliosides in human nerves plays a crucial role in the pathogenesis of GBS and MFS. Therefore, we first studied Campylobacter genes involved in LOS biosynthesis. We hypothesized that polymorphism in the LOS biosynthesis genes determines LOS structure and thereby the capability of a C. jejuni strain to induce a specific anti-ganglioside antibody response and clinical symptoms of GBS and MFS. Next, we aimed at the identification of potential genetic markers for GBS outside the LOS biosynthesis genes. Only a small proportion of infections with C. jejuni strains that express ganglioside mimics are followed by GBS or MFS. Therefore, it is likely that other pathogen- and/or host-related factors are also important for the development of neuropathy. In Chapter 2, we determined the types of LOS biosynthesis gene locus in our neuropathy-associated and control strains to identify potential GBS marker genes. We constructed gene knock-out mutants to investigate the role of these genes in ganglioside mimicry and induction of anti-ganglioside antibodies. In Chapter 3, we analyzed the individual LOS biosynthesis genes with PCR-RFLP to investigate the presence of additional markers for GBS. Chapter 4 describes how a C. jejuni strain may have acquired a GBS-related LOS biosynthesis locus. In Chapter 5 we investigated whether co-infections with multiple C. jejuni-strains occur in GBS patients and we further characterized these strains. In Chapter 6 we assessed the relationship between genetic polymorphism in LOS genes, the exact LOS structures as determined by mass-spectrometry techniques and clinical symptoms in the patients. Knowledge of the exact LOS structures enabled us to investigate the origin of antibodies against ganglio! side complexes (Chapter 7). Finally, we used high-throughput AFLP analysis, a genome-wide genotyping technique, to investigate the presence of GBS markers located outside the LOS biosynthesis gene locus (Chapter 8).
|Guillain-Barré Syndrome, auto-immune, campylobacter jejuni, lipo-oligosaccharides, molecular mimicry|
|A.F. van Belkum (Alex)|
|Erasmus MC: University Medical Center Rotterdam|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Godschalk, P.C.R. (2007, March 28). Campylobacter jejuni and the Guillain-Barré Syndrome: the role of bacterial genetic polymorphisms. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/9320