Worldwide Population Dynamics of Salmonella Saintpaul: Outbreaks, Epidemiology, and Genome Structure

Background/Objectives: Salmonella Saintpaul (SSa) is increasingly linked to foodborne outbreaks in Brazil and globally. Despite its rising public health significance, its epidemiology, genomic diversity, and pathogenic potential remain underexplored. This study addresses these gaps through a comprehensive global analysis of SSa population dynamics, outbreak patterns, and genetic structures, along with an in-depth phenotypic and genomic characterization of strain PP_BR059, isolated from a hospitalized patient in Ceará, Brazil. Methods: We analyzed 1,953 publicly available SSa genomes using core-genome multi-locus sequence typing (cgMLST), antimicrobial resistance (AMR) profiling, pan-genome analysis, and phylogenetic inference. A genome-wide association study (GWAS) identified genetic determinants of virulence and AMR. The invasiveness and intracellular survival of PP_BR059 were assessed using in vitro macrophage infection assays, while whole-genome sequencing (WGS) provided genetic insights. Results: Phylogenetic analysis identified 49 sequence types (STs), with ST-50 (787 genomes) and ST-27 (634 genomes) being most prevalent. ST-50 included all clinical strains from South America, including PP_BR059. AMR analysis showed 60% of SSa genomes were pan-susceptible, while ST-27 had the highest proportion of AMR strains. GWAS revealed distinct evolutionary lineages within ST-50 and ST-27. PP_BR059 exhibited lower macrophage invasion (3.82%) but significantly higher intracellular survival at 2 h (68.72%) and 20 h (25.68%) post-infection. WGS confirmed a pan-susceptible AMR profile and plasmid absence. Conclusions: This study highlights SSa’s global dissemination, evolutionary trends, and pathogenic variability, emphasizing the need for molecular surveillance to inform public health interventions.