Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1134371 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29773379_1.fastq.gz | Fastqsanger.gz | |||
| SRR29773379_2.fastq.gz | Fastqsanger.gz |
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Project description:Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely-related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). We hypothesised that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites (TSS) of the ST313 strain D23580, and searched for a gene expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance and modulated virulence in the chicken infection model. We propose that high levels of expression PgtE of by African S. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection. Our finding of a functional role for an extra-genic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on non-coding regions of the genome.
2017-12-15 | GSE108104 | GEO
Project description:We used microarrays to detail the global programme of gene expression in human macrophages infected in vitro with HIV-1 or not and then subjected to contact with Salmonella Typhimurium ST313 or ST19 strains; we identified distinct classes of differentially regulated genes during this process
2024-07-09 | GSE116803 | GEO
Project description:Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo.
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Project description:Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo.
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Project description:Salmonella Typhimurium ST313 is associated with invasive nontyphoidal salmonellosis (iNTS) disease in sub-Saharan Africa. Using ST313 isolate, D23580, and the well-characterized ST19 isolate 4/74, that causes gastroenteritis across Europe, we generated transcriptomic data from sixteen infection-relevant in vitro conditions and during infection of murine macrophages (http://bioinf.gen.tcd.ie/cgi-bin/jay/salcom_v2.pl?db=salcom_africa_new_HL). The transcriptional response of the two S. Typhimurium pathovariants to environmental stress was broadly similar. Comparative gene expression analysis identified virulence and metabolic genes that were up/down-regulated in D23580 versus 4/74. Findings were backed up by proteomic analysis, with12 genes being differentially-expressed at both the transcriptional and protein levels including melA and cysS. The data led us to discover that the ablation of melibiose utilization was caused by 3 SNP mutations in D23580 and to identify a novel plasmid-maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase. Our functional transcriptomic analysis represents a powerful tool for identification of key phenotypic differences between bacterial pathovariants.
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Project description:FabR ChIP-chip on Salmonella enterica subsp. enterica serovar Typhimurium SL1344 using anti-Myc antibody against strain with chromosomally 9Myc-tagged FabR (IP samples) and wildtype strain (mock IP samples)
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Project description:Investigation of gene expression level changes in Salmonella typhimurium LT2 TA100 upon exposure to C60, compared to unexposed controls. The mutations engineered into this strain make it susceptile to mutagenic compounds. The Salmonella typhimurium TA100 strain used in this study is further described in Pedersen P, Thomsen E, Stern RM. 1983. Detection by Replica Plating of False Revertant Colonies Induced in the Salmonella Mammalian Microsome Assay by Hexavalent Chromium. Environmental health perspectives 51: 227-230.
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