Integrated metabolomics and transcriptomics reveal the adaptive responses of Salmonella enterica serovar Typhimurium to thyme and cinnamon oils

Essential oils (EOs), such as thyme (Thy) and cinnamon (Cin) oils, present promising antibacterial properties against foodborne pathogens (e.g., Salmonella enterica serovar Typhimurium). However, the food matrix might result in sublethal EO stress, and little information about direct and/or cross-resistance development after sublethal EO exposure is available. This study revealed that S. Typhimurium under sublethal Thy and Cin (50% minimum inhibitory concentration, MIC50) treatments exhibited a lower growth rate and an extended lag phase. EO adapted cells showed direct-resistance to subsequent lethal EO treatment, and cross-resistance to thermal (58 °C) and oxidative (hydrogen peroxide, 50 mmol/L) stresses. Metabolomics analysis revealed changes of 47 significant metabolites (variable importance in projection > 1, false discovery rate (FDR) < 0.05), including lipids, oligopeptides, amino acids, nucleotide related compounds, and organic acids. Metabolic pathways, such as aminoacyl-tRNA biosynthesis, were shown to be involved in EO adaptation. Furthermore, a transcriptomics study identified 161 differentially expressed genes (DEGs, fold change > 2, FDR < 0.05) in MIC50 Thy treated cells, while more DEGs (3 2 4) were screened from the MIC50 Cin group. The integrated omics analysis allowed us to speculate on the molecular mechanisms. Under harsher Thy stress, S. Typhimurium cells adopted a conservative strategy to survive. By contrast, more radical responses were observed during Cin adaptation. In conclusion, the food industry should be more cautious in the use of EOs because sublethal EO stress might result in the development of resistance.