Phylogeographic clustering of Salmonella enterica serovar Mississippi in the Southeastern United States indicates regional transmission pathways

Salmonella enterica subspecies enterica serovar Mississippi ( S . Mississippi) is a polyphyletic serovar endemic in Australia, New Zealand, the United Kingdom, and the United States (USA). From 2018 to 2024, it was the 13 ^th most frequently reported clinical Salmonella serovar in the USA. Its incidence in the USA is geographically focused on the Southeast. From 2018 to 2024, 78% of all S. Mississippi cases in the USA occurred in Southeastern states. The objective of this study was to determine the phylogeographic patterns of clinical S. Mississippi in the Southeastern USA using clinical S. Mississippi isolate sequencing data and metadata from ten state public health laboratories in the region. The resulting phylogeny, based on core single nucleotide polymorphism (SNP) differences, showed that S. Mississippi has five major clades (Ai, Aii, Bi, Bii, C), four of which are consistent with the results of previous studies. Clade Ai, which comprised 99% of study isolates, was systematically divided into seven subclades. County-level mapping of the clade Ai isolates revealed distinct geographical distributions at the clade and subclade levels. For example, subclade Ai1 was predominantly identified along the East Coast, while subclade Ai3 was primarily found in Western Tennessee. Simple linear regression showed a significant positive association (p < 0.01) between isolate-to-isolate genomic distance (SNP differences) and county-to-county geographic distance (km) at the clade and subclade levels. These findings provide insight into the transmission of S. Mississippi and may inform public health hypothesis generation.