Role of a single noncoding nucleotide in the evolution of an epidemic African clade of <i>Salmonella</i>

Abstract

<i>Salmonella enterica</i> 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 <i>Salmonella</i> genomes has revealed that ST313 is closely related to the ST19 group of <i>S</i> Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African <i>Salmonella</i> from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of <i>Salmonella</i> We identified a SNP in the promoter of the <i>pgtE</i> gene that caused high expression of the PgtE virulence factor in African <i>S.</i> 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 PgtE expression by African <i>S</i> Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.