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Genomic Study Points to Stability in Enteric Fever-Causing Salmonella Lineage

NEW YORK (GenomeWeb) – Using genome sequences for thousands of Salmonella enterica isolates — including an 800-year-old Norwegian sample — researchers from the University of Warwick, the University of Copenhagen, and elsewhere demonstrated that an invasive S. enterica lineage called Para C has remained relatively genetically stable over its history.

"Our analyses show that reconstructing the long term evolutionary history of bacterial pathogens benefits dramatically from comparisons of metagenomic data from ancient samples with population genetic data from present-day bacteria," senior author Mark Achtman, a bacterial population genetics researcher at the University of Warwick, and his colleagues wrote in a study published today in Current Biology.

Achtman and his team began by doing metagenomic sequencing on bone and tooth samples from a woman known as SK152, who died when she was around 19 to 24 years old and was buried in present-day Norway an estimated 800 years ago. The resulting sequences were used to put together more than a dozen partial or more complete genomes, including a draft S. enterica genome dubbed Ragna.

"This is the first time that any Salmonella have been found in old human remains in Europe, which is surprising because other Salmonella are more common today," Achtman said in a statement.

With a phylogenetic analysis based on more than 711,000 SNPs in the Ragna genome and another 2,964 S. enterica genome sequences, the researchers found that the Paratyphi C serovar behind SK152's apparent death from septicemia and enteric fever is part of a broader Para C lineage. This broader lineage contains several other S. enterica serovars, which cause disease in domestic pigs and wild boars.

The team then sequenced 219 more S. enterica representatives from the Para C lineage, drawing from samples in the EnteroBase database and the Pasteur Institute's strain collection. These sequences made it possible to distinguish core and pan-genome sequences, while providing a more detailed look at serovars and sublineages within Para C. While the pan-genome appears to have remained relatively stable, the researchers suggested that the presence or absence of two pathogenicity islands — SPI-7, which contains a capsular polysaccharide gene, and SPI-6, which codes for a secretion system-coding gene — may have influenced historical shifts in host-specificity for specific serovars.

Meanwhile, the team also used substitution rate data to estimate that the most recent common ancestor for S. enterica bugs in the Para C lineage likely arose in Europe roughly 4,000 years ago. This suggested that the advent of a Paratyphi C lineage might have involved bugs that jumped to humans from pigs domesticated in the region.

"The close relationship between clades of the Para C lineage that differ in host specificity triggered intriguing speculations about historical host jumps during the Neolithic period between humans and their domesticated animals," Achtman and his co-authors concluded. "Our results also indicate that both the core and accessory genome of bacterial pathogens can be remarkably stable over millennia, and that much of the dramatic variation between extant genomes represents transient genetic fluctuation, whose evolutionary relevance to ecological fitness is uncertain."

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