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 13th 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. IMPORTANCEThis study enhances understanding of S. Mississippi transmission pathways and reveals localized phylogeographic clustering within the Southeastern USA. Classification of this serovar with consideration to geographical clustering may improve surveillance, investigation, and control efforts. Geographical clustering of this serovar within this region suggests local or regional transmission pathways and enzootic reservoirs, which could be related to environmental or regional food exposures. Identifying possible environmental sources, enzootic reservoirs, or climate factors contributing to human infection with this serovar within the Southeastern USA could lead to prevention recommendations. Knowledge of exposure patterns for S. Mississippi may facilitate development and implementation of targeted control strategies and interventions locally that can limit further exposure and prevent illness.