*Salmonella enterica* is a significant cause of foodborne illness worldwide, with pork and pigs being major sources of infection. While the role of intensive farming and global trade in transforming the pig industry is well-established, the impact on the evolution and spread of *S. enterica* remains poorly understood. This research addresses this gap by examining the population dynamics, antimicrobial resistance (AMR) gene acquisition, and global transmission of pig-enriched *S. enterica* populations. The study's importance lies in its contribution to the 'One Health' strategy, emphasizing the interconnectedness of human, animal, and environmental health. Understanding how modern agriculture influences the evolution of zoonotic pathogens like *S. enterica* is crucial for developing effective prevention and control measures. The rise of centralized industrial pork production in Europe and the United States, representing a significant portion of global pork trade, presents a unique opportunity to examine the role of industrialization in pathogen evolution and spread. This study leverages the wealth of genomic data now available to gain insights into these dynamics, ultimately improving our understanding and ability to mitigate the risks associated with *S. enterica* infections.

Previous research has highlighted the role of pigs in mediating *Salmonella* transmission and outbreaks. Studies have also explored the impact of intensive farming and globalization on agricultural practices. However, a comprehensive analysis integrating these factors to understand the evolution of *S. enterica* within the framework of the 'One Health' initiative has been lacking. This paper builds upon existing knowledge by examining a large-scale dataset of *S. enterica* genomes to provide a comprehensive view of the population dynamics, AMR gene accumulation, and global transmission patterns of pig-enriched *Salmonella* serovars. It directly addresses the limited understanding of how modern agriculture has shaped the evolution of this important zoonotic pathogen.

The researchers utilized data from EnteroBase, a comprehensive database of bacterial genomes, to identify pig-enriched *S. enterica* populations. They focused on nine populations, each with >40% of strains derived from pigs and pork, and analyzed over 9,000 genomes. Phylogenetic analyses, including maximum-likelihood and Bayesian methods, were employed to reconstruct evolutionary relationships, infer ancestral host associations, and estimate the timing of key events like host jumps and population expansions. Antimicrobial resistance genes (ARGs) were identified using bioinformatic tools like AMRfinder, while gene disruption was assessed using PEPPAN. The study also incorporated data from the Harvard database on global pork trade to assess the correlation between pork trade patterns and the geographic spread of pig-enriched *S. enterica*. Specifically, they sequenced the genomes of 78 *S. enterica* serovar Choleraesuis strains (63 from Europe, 15 from China), integrating them with public data to create a global dataset of 757 genomes. The analysis involved sophisticated techniques including: whole-genome sequencing, phylogenetic reconstruction (maximum likelihood and Bayesian), identification of antimicrobial resistance genes, and analysis of pseudogenes and disrupted genes. They employed statistical methods like Simpson's diversity index and correlation analysis to assess patterns of genetic diversity and geographic spread. Uniform Manifold Approximation and Projection (UMAP) was used for visualizing high-dimensional data, allowing for a comparative analysis of pathogen transmission patterns and trade data. The study also conducted date randomization tests to evaluate the presence of temporal signals in the evolutionary history of the *Salmonella* populations.

The analysis revealed that pigs have become a primary source of *S. enterica* transmission to other hosts, particularly humans. Europe emerged as the major genetic repository of *Salmonella* serovar Choleraesuis, with high genetic diversity observed in Western and Northern Europe. Intensive pig farming practices were associated with increased accumulation of ARGs in *Choleraesuis* strains from pigs and humans compared to those from wild boars. The study identified a peak in international transmissions of *Choleraesuis* between the 1950s and 1980s, coinciding with the expansion of global agricultural trade. Analysis of nine pig-enriched *S. enterica* populations showed that most experienced host transfers into pigs after the 1930s, with pigs becoming the main source of recent transmissions (past 50 years). UMAP analysis demonstrated a strong correlation between the global pork trade and the transmission of pig-enriched *Salmonella*, particularly for processed pork products. The study showed that Europe and the Americas serve as central hubs for the dissemination of these pathogens globally. *Salmonella* serovar Choleraesuis strains displayed a high prevalence of resistance against aminoglycoside, sulfonamide, tetracycline and beta-lactam antibiotics, often used in intensive farming. Quinolone resistance, an urgent threat, was also prevalent in human and pig strains. The presence of colistin resistance genes *mcr-1* and *mcr-3* in strains from multiple countries highlighted their global spread.

The findings underscore the profound impact of modern agricultural practices on the evolution and dissemination of *S. enterica*. The centralized industrialization of pork production in Europe and America has created conditions conducive to the emergence, expansion, and global spread of pig-enriched *Salmonella*. The strong correlation between pork trade and pathogen transmission highlights the importance of considering trade routes in disease surveillance and control. The increased accumulation of ARGs in strains from pigs and humans, particularly compared to wild boars, emphasizes the role of antimicrobial use in animal agriculture in driving AMR. The observed temporal patterns in *Choleraesuis* transmission align with historical developments in intensive farming and globalization, reinforcing the links between agricultural practices and pathogen evolution. The study's implications for public health are significant, suggesting the need for a 'One Health' approach to address the challenges posed by this zoonotic pathogen.

This study demonstrates the critical role of modern, centralized pork production in the global dissemination of *Salmonella enterica*. Intensive farming practices, coupled with global trade, have driven the emergence of pig-enriched *Salmonella* populations, increased AMR, and facilitated widespread transmission. Future research should focus on detailed investigations into local transmission patterns, including the role of wild boar populations and country-wide agricultural transportation. Improving surveillance of *Salmonella* in both domestic and wild pig populations is crucial, along with further investigation into the effectiveness of current control measures. Strategies addressing the interconnectedness of animal husbandry, food production, and human health are vital to mitigating the ongoing threat posed by *Salmonella* infections.

The study acknowledges potential sampling bias due to the reliance on publicly available genomic data, which are often skewed towards developed countries. The genetic diversity of pig-enriched *Salmonella* populations in many developing countries remains under-sampled. While downsampling was used to mitigate this bias, it could introduce different biases. Further limitations include the lack of sufficient data for the thorough analysis of local transmissions due to agricultural transportation or wild boar movement. The data on antibiotic use across different countries and regions was limited.