Support data for "Integrative analysis of fitness and metabolic effects of a large multidrug-resistant plasmid in Salmonella across diverse serovar"

Plasmids, particularly those of the IncHI2 type, are key drivers of multidrug resistance in Salmonella. However, the fitness costs imposed by multidrug-resistant (MDR) IncHI2 plasmids across different serovars and the underlying mechanisms remain poorly understood. Here, we report that carriage of the MDR IncHI2 plasmid pMDRHI2 imposes a significant fitness cost that varies considerably across Salmonella hosts. This phenotypic variation is accompanied by pronounced serovar-specific differences in both transcriptional and metabolic reprogramming. Notably, despite this heterogeneity, plasmid carriage consistently perturbed the expression of chromosomal loci involved in propanediol utilization (pdu), ethanolamine utilization (eut), and sulfur and glycerophospholipid metabolism, though in a strain-dependent manner. Integrative analysis of transcriptomic and metabolomic data further identified coordinated alterations in propanoate metabolism, purine metabolism, and the sulfur relay system in specific plasmid-carrying strains. Both addition of differentially-expressed metabolites (DEMs) assay and correlation analysis of transcriptomic and metabolomic data revealed that the observed fitness costs are linked to distinct metabolic lesions: dysregulated propanoate metabolism in the S. 1,4,[5],12:i:- background, and impaired aerobic respiration or redox homeostasis in S. Indiana and S. Enteritidis. Collectively, these findings demonstrate that the fitness burden imposed by MDR IncHI2 plasmid carriage is dictated by serovar-specific host factors and arises from plasmid-mediated remodeling of central metabolic pathways.