Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1148124 | 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:The emergence of extensively drug-resistant Shigella sonnei in Vietnam
| PRJEB30967 | ENA
Project description:"Shigella spp. are the causative agents of shigellosis, which remains a major cause of death in children under the age of five. Shigellosis is marked by fever and leads to hemorrhagic diarrhea; Shigella bacteremia are reported in more severe cases. These clinical features strongly suggest that Shigella survive to plasma exposure, although it has not been previously investigated at a molecular level. In this report, we confirmed in a guinea pig model of shigellosis that local hemorrhages were induced by S. flexneri 5a and S. sonnei and we demonstrated that Shigella reached CD31+/CD34+ blood vessels within the mucosa during late infection stage and further disseminated in the blood circulation. These results confirmed the exposition of Shigella to plasma components during its virulence cycle, from the hemorrhagic colonic mucosa to the blood circulation. We demonstrated that all tested Shigella strains survived to plasma exposure in vitro and we have shown that Serine Protease Autrotransporters of Enterobacteriaceae (SPATEs) are essential for Shigella dissemination within the colonic mucosa and in the blood circulation. We confirmed that SPATEs were expressed and secreted within poorly oxygenated environments encountered by Shigella from hypoxic foci of infection to the blood circulation. We have further demonstrated that SPATEs promoted the survival of Shigella to plasma exposure, by cleaving the complement 3 component (C3), hence impairing the complement system activation."
2024-08-27 | PXD048033 | Pride
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:global fluoroquinolone resistant Shigella sonnei genomic study
| PRJNA320210 | ENA
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:BACKGROUND: Infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging worldwide. We investigated an outbreak of severe CA-MRSA infections in children following out-patient vaccination. METHODS AND FINDINGS: We carried out a field investigation after adverse events following immunization (AEFI) were reported. We reviewed the clinical data from all cases. S. aureus recovered from skin infections and from nasal and throat swabs were analyzed by pulse-field gel electrophoresis, multi locus sequence typing, PCR and microarray. In May 2006, nine children presented with AEFI, ranging from fatal toxic shock syndrome, necrotizing soft tissue infection, purulent abscesses, to fever with rash. All had received a vaccination injection in different health centres in one District of Ho Chi Minh City. Eight children had been vaccinated by the same health care worker (HCW). Deficiencies in vaccine quality, storage practices, or preparation and delivery were not found. Infection control practices were insufficient. CA-MRSA was cultured in four children and from nasal and throat swabs from the HCW. Strains from children and HCW were indistinguishable. All carried the Panton-Valentine leukocidine (PVL), the staphylococcal enterotoxin B gene, the gene complex for staphylococcal-cassette-chromosome mec type V, and were sequence type 59. Strain HCM3A is epidemiologically unrelated to a strain of ST59 prevalent in the USA, although they belong to the same lineage. CONCLUSIONS: We describe an outbreak of infections with CA-MRSA in children, transmitted by an asymptomatic colonized HCW during immunization injection. Consistent adherence to injection practice guidelines is needed to prevent CA-MRSA transmission in both in- and outpatient settings. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-45
2009-01-16 | E-BUGS-45 | biostudies-arrayexpress