Shigella sonnei Switzerland
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ABSTRACT:
PROVIDER: PRJEB23646 | ENA |
REPOSITORIES: ENA
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Project description:Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.
2019-11-19 | GSE140544 | GEO
Project description:Expression of type III secretion system (TTSS), a major determinant of virulence in Shigella, is markedly inhibited in a deletion mutant (cpxA) of the CpxAR two-component sensor at the level of post-transcriptional processing of the second TTSS regulator, InvE. A novel mutant of rodZ, which encodes a cytoskeletal protein involved in maintaining the rod-shaped morphology of bacilli, was isolated in a screen for mutations that restored TTSS expression in a cpxA mutant. The rodZ mutants of Shigella sonnei efficiently expressed InvE at 30°C, a temperature at which expression is normally repressed through temperature-dependent post-transcriptional regulation. Consistent with a marked increase in invE mRNA stability in the rodZ mutant, purified RodZ strongly bound to an invE RNA probe. Functional domain mapping indicated that the RNA binding activity of RodZ was dependent on a short basic region (KRRKKR) and multimer formation. Electron microscopy revealed that RodZ multimers formed filamentous superstructures, similar to another bacterial cytoskeletal protein, MreB. Our results indicate that RodZ functions as a novel membrane-bound RNA binding protein that provides a scaffold for post-transcriptional regulation. Phenotypic analysis of deletion mutant for RNA binding protein RodZ. The mutants analyzed in this study are further described in Jiro Mitobe, Itaru Yanagihara, Kiyouhisa Ohnishi, Akira Ishihama and Haruo Watanabe 2010. Bacterial cytoskeleton RodZ regulates post-transcriptional processing of Shigella type III secretion system. EMBO-J ( in submission). Four samples. Wild-type Shigella sonnei strain and the deletion mutant of rodZ gene, with or without rifampicin treatment for kinetics of mRNA stability.
2011-03-31 | E-GEOD-21051 | biostudies-arrayexpress
Project description:Shigella sonnei as an enteric pathogen, can benefit from outcompeting gut commensals such as Escherichia coli and there can be several mechanisms that assist in interbacterial competition. It is, therefore, important to understand these mechanisms as they provide insights into the interactions of these pathogens in the complex environment they exist. We used our novel Bulk Phenotyping of Epidemiological Replicates (BPER) pipeline combined with bacterial Genome Wide Association Studies (GWAS) on a previously described real-world collection of S. sonnei isolates (n=165) to demonstrate the vital role that colicins could have played in shaping the observed epidemiology of S. sonnei. We then used targeted mass spectrometry on representative S. sonnei isolates to detect colicin sequences in cell free supernatants, which further validated our BPER results to suggest the vital role of colicins. Here, we also introduce BPER as an epidemiologically relevant way of phenotypic testing in the laboratory where the phenotypic results can be interpreted with much more relevance to the effects of those phenotypes in natural settings.
2023-10-24 | PXD036656 | Pride