With 3.4 million infections each year, invasive non-Typhoidal Salmonella (iNTS) is a major cause of illness worldwide. In Sub-Saharan Africa, which carries the heaviest iNTS burden, bloodstream infections with iNTS Salmonella enterica serovar Typhimurium are causing ~388,000 deaths annually. Co-infection with HIV or malaria in adults, and a young age (<5 years) are known risk factors.
Whole-genome sequencing of iNTS strains revealed a new sequence type (ST313), that showed high similarity to the well-studied non-invasive S. Typhimurium ST19 responsible for gastroenteritis. The core genomes of two representative strains of ST313 (D23580) and ST19 (4/74) differ by ~1,000 SNPs. We hypothesised that phenotypic differences between strains D23580 and 4/74 would reveal the properties of ST313 responsible for invasive human disease.
The primary transcriptomes of D23580 and 4/74 were defined by a combined RNA-seq/dRNA-seq approach1, and we used the transcriptomic data to compare expression of bacterial promoters. Our analysis led us to identify a single core genome SNP responsible for the up-regulation of a promoter in strain D23580 that controlled the expression of a S. Typhimurium virulence factor.
We propose that the ability of S. Typhimurium ST313 to express high levels of this virulence factor contributes to bacterial survival during systemic infection, and has contributed to the pan-African epidemic of bloodstream infection.