Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1117046 | 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 flexneri 2a and Shigella sonnei were genetically modified to shed large quantities of outer membrane blebs. The blebs, called Generalized Modules for Membrane Antigens (GMMA), were purified and the protein content was estimated using the label-free iBAQ procedure. There were 2308 proteins identified, 660 in GMMA and 2239 in bacteria, of which 288 (GMMA) and 1695 (bacteria) were common to both S. flexneri 2a and S. sonnei. Protein abundances were classified according to the predicted localization. Predicted outer membrane or periplasmic proteins constituted 95.7% and 98.7% of the protein mass of S. flexneri 2a and S. sonnei GMMA, respectively. Among the remaining proteins, small quantities of ribosomal proteins collectively accounted for more than half of the predicted cytoplasmic protein impurities in the GMMA. In GMMA, the outer membrane and periplasmic proteins were enriched 13.3-fold (S. flexneri 2a) and 8.3-fold (S. sonnei) compared to their abundance in the parent bacteria. Both periplasmic and outer membrane proteins were enriched similarly, suggesting that GMMA have a similar surface to volume ratio as the surface to periplasmic volume ratio in these mutant bacteria. Results in S. flexneri 2a and S. sonnei showed high reproducibility indicating a robust GMMA-producing process.
2016-01-12 | PXD002517 | Pride
Project description:Interferons (IFNs) are vital weapons in the arsenal of immune mediators produced in response to infection. We showed that Shigella sonnei blocks signaling and interferon-stimulated genes (ISGs) downstream of all families of IFN via secreted effectors of the OspC family. Notably, Ospc1 and OspC3 strongly block the IFN response. This project aims at investigating the cellular signaling pathways that are impacted by OspC1 and OspC3 with or without IFN stimulation and at clarifying whether observed changes in ISGs expression are general or specific to some ISGs.
2022-11-02 | GSE200447 | GEO