Population structure and ongoing microevolution of the emerging multidrug-resistant Salmonella Typhimurium ST213

Salmonella enterica serovar Typhimurium ST213 is an emergent multidrug-resistant sequence type associated with the food chain, and gastrointestinal and invasive infections in North America. Here, we applied genomic and phenotypic analyses to illustrate the diversity and evolution of sequence type ST213. The population structure and evolutionary history of ST213 strains, particularly the North American isolates (NA-ST213) distinguish them from other S. Typhimurium sequence types, including European ST213 strains. NA-ST213 isolates were distributed in four co-circulating lineages with distinct multidrug resistance profiles and unique phage and CRISPR spacers patterns that could have shaped their local microevolution. Compared to the SL1344 reference strain, NA-ST213 demonstrated reduced adherence and internalization in cultured eukaryotic cell lines but exhibited more efficient replication and intracellular survival. This study underscores the relevance of studying an emergent S. Typhimurium sequence type and the events leading to its diversification beyond the well-characterized reference strains and worldwide predominant sequence types. However, it must also serve as a cautionary tale of the potential health risk the NA-ST213 may represent; particularly when there is a close relationship with pandemic sequence types such as the monophasic ST34.