Mobile genetic elements potentially drive adaptive evolution of pork-derived multidrug-resistant Salmonella Derby...

Salmonella Derby (S. Derby) is transmitted to humans through contaminated pork products. S. Derby ST40, with multidrug resistance (MDR) and extensive drug resistance, poses major food safety and public health challenges. By integrating antimicrobial susceptibility testing, phylogenetic analysis, phylogeographic reconstruction, pan-genomics, and pan-genome-wide association study, we investigated adaptive evolution and transmission dynamics of antibiotic resistance in S. Derby ST40 (71 isolates from livestock and 1572 global isolates from humans, food, and environment). Globally, S. Derby ST40 strains (69.36 % pork-derived) were divided into six clades. bla_OXA-1-carrying MDR Clade VI evolved in China from Clade II Clade VI carried about 19 resistance genes; its MDR primarily resulted from combined effects of resistance genes in chromosomal MDR regions and mobile genetic elements (MGEs), accumulating via horizontal gene transfer. S. Derby ST40 accessory genes contained abundant recombinases associated with MGEs and resistance genes. Pork-derived MGEs and chromosomal MDR variable regions may drive Clade VI's evolution. Molecular clock analysis indicated that S. Derby ST40 originated in the United States in 1939, and Clade VI diverged from Clade II in China around 1979. Clade VI engaged in global antimicrobial resistance network via intercontinental transmission; China emerged as a main transmission hub in the 21st century. Globally circulating pork- and poultry-derived strains demonstrate more resistance genes than human-derived strains, indicating that animal husbandry and animal food production chains are resistance gene reservoirs. Strengthening antibiotic regulation in livestock farming may curb resistance gene dissemination within food chains, and a One Health governance framework may prevent and control cross-border MDR bacterial transmission.