Salmonella Agona inside and outside the French borders: phylogenomic diversity, plasmidome, resistome and virulome

Salmonella enterica serotype Agona (S. Agona) is a globally distributed foodborne pathogen associated with diverse hosts, environments, and foodborne outbreaks. We investigated its population structure, global dissemination, and the genetic determinants underlying the ecological adaptation and epidemiological success of strains implicated in nationwide alerts in France in 2005 and 2017. A total of 4202 genomes from isolates collected worldwide between 1952 and 2025 were analyzed, including 141 newly sequenced genomes representative of agri-food sectors in France. Whole-genome analyses confirmed the polyphyletic nature of S. Agona, while cgMLST hierarchical clustering at the HC900 level identified two major genomic lineages differing in type VI secretion system (T6SS) patterns and the presence of Salmonella pathogenicity island 17 (SPI-17). The dominant lineage (ST13) accounted for approximately 99% of genomes and displayed broad distribution across hosts and ecological niches worldwide. Despite core genome conservation, fine-scale HC5 clustering revealed substantial microdiversity with 1771 clusters, including 229 identified among isolates from France, 183 of which were unique to the country. Phylogenetic analysis of 233 human and agri-food isolates from France suggested complex transmission pathways between environmental, food, and human reservoirs and demonstrated that the 2017 infant formula outbreak in France originated from direct descendants of the 2005 outbreak clone. Accessory genome analysis revealed genes associated with tolerance to metals, biocides, and antimicrobials, two independently acquired Salmonella genomic island-4-like elements, and 133 predicted plasmids, collectively encoding 26 carrying antimicrobial resistance genes. These findings provide new insights into the evolution, ecological versatility, and public health significance of S. Agona.