Abstract
Salmonella enterica serovar Braenderup (S. enterica ser. Braenderup) is an important clinical serovar in the United States. This serovar was reported by the CDC in 2017 as the fifth most common Salmonella enterica serovar associated with outbreaks in the United States, which have been linked to both fresh produce and food animal products. The goals of this study were to compare the relatedness of human clinical isolates from southeastern USA (Tennessee (n = 106), Kentucky (n = 48), Virginia (n = 252), South Carolina (n = 109), Georgia (n = 159), Alabama (n = 8), Arkansas (n = 26), and Louisiana (n = 91)) and global clinical (n = 5,153) and nonclinical (n = 1,053) isolates obtained from the NCBI. Additionally, we also examined the population structure of S. enterica ser. Braenderup strains (n = 3,131) on EnteroBase and found that all the strains of this serovar are associated with a single cgMLST eBurst group (ceBG 185), confirming that this serovar is monophyletic. We divided the S. enterica ser. Braenderup population into two clades (Clade I and Clade II) and one clade group (Clade Group III). The composition of distinct environmental isolates in the clades differed: Clade I was significantly associated with produce (90.7%; P < 0.0001) and water, soil, and sediment (76.9%; P < 0.0001), and Clade II was significantly associated with poultry environments (62.8%; P < 0.0001). The clade-specific gene associations (e.g., Clade I-associated competence proteins and cytochrome_c_asm protein and Clade II-associated heme-exporter protein and dimethyl sulfoxide [DMSO] reductase-encoding genes) provide potential insights into possible mechanisms driving environmental adaptation and host-pathogen interaction. Phylogenetic analyses identified 218 molecular epidemiological clusters in the current study, which represented a greater proportion of potentially outbreak-related isolates than previously estimated. IMPORTANCE: This study provides insights into the genomic diversity of S. enterica ser. Braenderup by revealing distinct clade-specific source attribution patterns and showing that a greater proportion of isolates were associated with epidemiological clusters based on the genomic relatedness than previously estimated. Specifically, we analyzed the diversity of human clinical isolates from southeastern USA and compared them with the global clinical and nonclinical isolates. Our analysis showed different clades of S. enterica ser. Braenderup linked to different environments, providing insights on the potential source of human sporadic infection and outbreaks. These findings can enhance public health surveillance and response strategies targeting S. enterica serovar Braenderup by expanding our understanding of potential transmission pathways and the genomic diversity of clinical and environmental isolates.