# Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne Staphylococcus aureus

## TL;DR

This study shows that a key metabolic enzyme in Staphylococcus aureus helps it resist antibiotics and survive in food environments, suggesting new ways to fight foodborne infections.

## Contribution

The study identifies pyruvate carboxylase (PycA) as a metabolic regulator critical for antimicrobial resistance and virulence in foodborne S. aureus.

## Key findings

- Deletion of pycA reduced resistance to β-lactams, aminoglycosides, and macrolides by 4- to 1024-fold.
- PycA deletion impaired biofilm formation by 23.24% and staphyloxanthin production by 22.32%.
- Proteomic analysis linked PycA to downregulation of TCA cycle, purine biosynthesis, and virulence factors like BlaZ.

## Abstract

Staphylococcus aureus, 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 S. aureus. In this study, a pycA 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 pycA 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 S. aureus resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference.