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

Zifeng Mai1, Jiahui Li1, Zeqiang Zhan1

  • 1State Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.

Foods (Basel, Switzerland)
|August 14, 2025
PubMed

Insights

Targeting pyruvate carboxylase (PycA) in Staphylococcus aureus significantly reduces its resistance to antibiotics and impairs biofilm formation. This metabolic enzyme is crucial for S. aureus survival in food systems.

Area of Science:

  • Food safety
  • Microbiology
  • Metabolic engineering

Background:

  • Staphylococcus aureus is a leading cause of foodborne illness.
  • Multidrug resistance and biofilm formation in S. aureus pose significant challenges.
  • Pyruvate carboxylase (PycA) is a key metabolic enzyme linking glycolysis and the TCA cycle, making it a potential therapeutic target.

Purpose of the Study:

  • To investigate the role of PycA in the virulence and antimicrobial resistance of S. aureus.
  • To explore PycA as a potential target for controlling S. aureus in food systems.

Main Methods:

  • Construction and phenotypic analysis of a pycA mutant in a foodborne methicillin-resistant S. aureus strain (ATCC BAA1717).
  • Proteomic analysis to identify metabolic and virulence factor changes.
  • Antimicrobial resistance assays, biofilm formation assays, and staphyloxanthin production measurements.

Main Results:

  • Deletion of pycA led to a 4- to 1024-fold reduction in resistance to multiple antibiotic classes.
  • pycA mutation resulted in a 23.24% decrease in biofilm formation and a 22.32% decrease in staphyloxanthin production.
  • Proteomics revealed downregulation of the TCA cycle, purine biosynthesis, surface adhesins, and beta-lactamase, linking PycA to S. aureus resilience.

Conclusions:

  • PycA is a critical metabolic regulator essential for S. aureus virulence and antimicrobial resistance in food environments.
  • Targeting PycA offers a promising strategy to combat foodborne staphylococcal infections through metabolic interference.
Keywords:
Staphylococcus aureusTCA cycleantimicrobial resistancebiofilmpurine metabolismpyruvate carboxylase

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