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Styphimurium_ST313

ABSTRACT: The role of the st313-td gene in virulence of Salmonella Typhimurium ST313

PROVIDER: PRJEB4869 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR359755.fastq.gz	Fastqsanger.gz
	ERR359756.fastq.gz	Fastqsanger.gz
	ERR359757.fastq.gz	Fastqsanger.gz
	ERR359758.fastq.gz	Fastqsanger.gz
	ERR359759.fastq.gz	Fastqsanger.gz

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The role of a single non-coding nucleotide in the evolution of an epidemic African clade of Salmonella

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.

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Expression data from in vitro HIV-1-infected macrophages responding to two SalmonellaTyphimurium bacteria

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

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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:Salmonella Typhimurium ST313 strain D23580_liv2

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