Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne .

, a major cause of foodborne illness globally, presents significant challenges due to its multidrug resistance and biofilm-forming capabilities. Pyruvate carboxylase (PycA), a metabolic master switch linking glycolysis and the tricarboxylic acid (TCA) cycle, is a potential target for controlling . In this study, a mutant was constructed and analyzed using phenotypic assays and proteomics to investigate its role in virulence and antimicrobial resistance. The results showed that deletion of in the foodborne methicillin-resistant strain ATCC BAA1717 resulted in a 4- to 1024-fold reduction in resistance to β-lactams, aminoglycosides, and macrolides; a 23.24% impairment in biofilm formation; and a 22.32% decrease in staphyloxanthin production, a key antioxidant essential for survival in oxidative food environments. Proteomic analysis revealed downregulation of the TCA cycle, purine biosynthesis, surface adhesins (FnbA/B, SasG), and β-lactamase (BlaZ), linking PycA-mediated metabolism to phenotypes relevant to food safety. These findings underscore the importance of PycA as a metabolic regulator crucial for resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference.