The SaeRS two-component system likely mediates the major dopamine-dependent regulation of virulence in Staphylococcus aureus ATCC 25,923

Abstract Staphylococcus aureus ( S. aureus )is an important foodborne pathogen. Host-derived catecholamines released under stress are known to influence bacterial pathogenic processes, including growth, virulence, biofilm formation. However, the role of dopamine in this context remains less well understood, particularly in S. aureus . In this study, we investigated the effects of dopamine on S. aureus ATCC 25,923 using a combination of phenotypic assays and multi-omics analyses. Dopamine was taken up by the bacteria and was associated with enhanced pathogenic phenotypes, including increased proliferation, toxin production, biofilm formation, motility, adhesion, and multidrug resistance. In a mouse infection experiment, dopamine treatment further increased bacterial colonization and organ invasion. Mechanistically, multi-omics analyses indicated that dopamine activates the SaeRS two-component system and is associated with the upregulation of virulence-related factors, adhesion-associated proteins, and membrane lipid synthesis pathways, along with increased activity in key metabolic processes such as the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Importantly, deletion of saeS markedly attenuated these dopamine-associated effects. Taken together, these findings suggest that dopamine likely influences S. aureus pathogenicity primarily through the SaeRS signaling pathway and provide insight into how host stress signals may contribute to bacterial infection.