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Rather than focusing on a comparison of the core genome, we used comparative transcriptomics to identify transcripts that were both expressed at different levels and associated with a distinct SNP in the promoter region. Typhimurium ST313 was linked to the altered expression of a core genome-encoded virulence factor. We investigated whether the emergence of the epidemic clade of S. Our challenge was to identify which, if any, of the >1000 SNPs that separate strains D23580 and 4/74 serve to differentiate the strains in terms of gene expression and phenotype. The strain 4/74 was isolated from a calf in the UK and is a well-characterised representative of S. Typhimurium ST313 lineage 2 is D23580, which was isolated from an HIV-negative Malawian child 5.
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We used a functional genomic approach to search for single nucleotide polymorphisms responsible for the increased virulence of S. ST313 exhibits a stealth phenotype during macrophage infection consistent with an immune evasion strategy that causes reduced levels of IL-1β cytokine production, apoptosis and Caspase-1-dependent macrophage death 10, 11. Typhimurium, ST313 is more resistant to complement-mediated killing by human serum 8, 9 and to macrophage-mediated killing 10. Compared with the ST19 group of gastroenteritis-associated S. Typhimurium isolated from patients in England and Wales are ST313, but lack the characteristic prophages BTP1 and BTP5 that are signatures of African ST313 lineages 7.Ĭertain virulence-associated phenotypes have been examined in ST313 strains. Co-infection with HIV or malaria infection and young age (4,000 genes, and their core genomes differ by about 1,150 SNPs 4. Typhimurium, ST313, is the primary cause of invasive non-typhoidal Salmonellosis (iNTS) across Africa, resulting in ∼388,000 deaths each year 1. Typhimurium) is one of the best understood bacterial pathogens, and a major cause of gastroenteritis globally.
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Salmonella enterica serovar Typhimurium ( S. 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. Typhimurium ST313 promotes bacterial survival and bacterial dissemination during human infection. We propose that high levels of expression PgtE of by African S.
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The PgtE protease is known to mediate systemic infection in animal models. 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 identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. 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 hypothesised that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. The core genomes of ST313 and ST19 vary by just 1000 single-nucleotide polymorphisms (SNPs). Typhimurium that cause gastroenteritis across the world. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely-related to the ST19 group of S. 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.