Project description:<p>Objective: Guillain barre syndrome (GBS) is a rare immune-mediated inflammatory disease of the complex peripheral nervous system. Long-term “silent infection” caused by changes in intestinal flora is potentially a contributing factor for immune-mediated inflammatory diseases, but the causative link between GBS and intestinal flora remains unclear. The present study aimed to characterize gut microbiome structure and estimate its association with the serum metabolic profile and in GBS. </p><p>Methods: Untargeted metabolomics profiling of serum, using liquid chromatography-mass spectrometry, and metagenomics sequencing of stool samples from a cohort of GBS and non-GBS subjects were performed to evaluate serum metabolic profiles and gut microbiome structure in GBS subjects relative to healthy controls. Pearson’s correlation analysis was used to estimate the correlations between the gut microbial abundance and serum metabolic profile. </p><p>Results: For intestinal microflora, Ligilactobacillus_salivarius, Klebsiella pneumonia, Enterocloster bolteae and Methanobrevibacter smithii were notably more abundant in GBS subjects, while Bacteroides sp., Roseburia hominis, and Paraprevotella xylaniphila decreased significantly. Metabolome data revealed that the gamma-aminobutyric acid (GABA) and secondary cholic acid metabolism were perturbed in GBS. GABA increased significantly, while secondary cholic acids as methyl deoxycholate, glycodeoxycholic acid, glycolithocholic acid, taurolithocholic acid and coprocholic acid, decreased significantly in GBS versus non-GBS controls. Metagenome data also revealed that GABA biosynthesis pathway was enriched, while secondary cholic acid metabolism pathways were decreased in gut microbes in GBS subjects. Correlation analysis revealed that changes in GABA were associated with altered gut microbes, such as Enterococcus species, Ligilactobacillus salivarius, Enterocloster bolteae and Methanobrevibacter smithii, and changes in secondary cholic acids were positively correlated with Bacteroides species and Roseburia species.</p><p>Conclusion: The well-known opportunistic pathogenic Klebsiella pneumonia and other special gut microbes significantly enriched in GBS. GABA and secondary cholic acid metabolism were significantly disturbed in GBS subjects and might be affected by the dysbiosis of gut microbial flora. These findings suggest that GABA may be a promising biomarker for the diagnosis of GBS and that modulation of gut microbiota might impact the clinical course of GBS.</p>
Project description:The purpose of this study was to identify Group B Streptococcus (GBS) genes that are controlled by the CiaR response regulator. Deletion of the GBS ciaR gene resulted in a significant decrease in intracellular survival within neutrophils, murine macrophages, and human BMEC, which was linked to increased susceptibility to killing by antimicrobial peptides, lysozyme, and reactive oxygen species. Furthermore, competition experiments in mice showed that wild-type GBS had a significant survival advantage compared to the isogenic ciaR mutant. Microarray analysis comparing gene expression between the wild-type and ciaR mutant strains revealed several CiaR-regulated genes that may contribute to GBS stress tolerance and subversion of host defenses.
Project description:The purpose of this study was to identify Group B Streptococcus (GBS) genes that are controlled by the CiaR response regulator. Deletion of the GBS ciaR gene resulted in a significant decrease in intracellular survival within neutrophils, murine macrophages, and human BMEC, which was linked to increased susceptibility to killing by antimicrobial peptides, lysozyme, and reactive oxygen species. Furthermore, competition experiments in mice showed that wild-type GBS had a significant survival advantage compared to the isogenic ciaR mutant. Microarray analysis comparing gene expression between the wild-type and ciaR mutant strains revealed several CiaR-regulated genes that may contribute to GBS stress tolerance and subversion of host defenses. Two cultures each of the wild-type GBS strain (COH1) and the isogenic ciaR mutant were grown in Todd-Hewitt broth to an optical density of 0.3. Cells were disrupted by shaking with glass beads and RNA was isolated by a Trizol method. A custom Affymetrix chip with a design based on the COH1 genomic sequence was used to analyze gene expression.
Project description:Streptococcus agalactiae (Lancefield’s group B Streptococcus, GBS) is a major bacterial species of genus Streptococcus and has medical and veterinary importance by affecting mainly humans (Maione et al., 2005; Johri et al., 2006), cattle (Keefe, 1997) and fish (Mian et al., 2009). The GBS is the most important pathogen for the Nile tilapia, a global commodity of the aquaculture sector, causing outbreaks of septicemia and meningoencephalitis (Hernández et al., 2009; Mian et al., 2009).