Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i>
<i>Staphylococcus aureus</i>, 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, i...
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2025-07-01
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| author | Zifeng Mai Jiahui Li Zeqiang Zhan Xiaorong Tian Wanwan Hou Mu He Chunlei Shi |
| author_facet | Zifeng Mai Jiahui Li Zeqiang Zhan Xiaorong Tian Wanwan Hou Mu He Chunlei Shi |
| author_sort | Zifeng Mai |
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| description | <i>Staphylococcus aureus</i>, 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 <i>S. aureus</i>. In this study, a <i>pycA</i> 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 <i>pycA</i> 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 <i>S. aureus</i> resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-6ddab3d5451f448f912b5374dc4deffd2025-08-20T03:36:06ZengMDPI AGFoods2304-81582025-07-011415256610.3390/foods14152566Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i>Zifeng Mai0Jiahui Li1Zeqiang Zhan2Xiaorong Tian3Wanwan Hou4Mu He5Chunlei Shi6State Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaState Key Laboratory of Microbial Metabolism, Department of Food Science & Technology, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China<i>Staphylococcus aureus</i>, 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 <i>S. aureus</i>. In this study, a <i>pycA</i> 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 <i>pycA</i> 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 <i>S. aureus</i> resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference.https://www.mdpi.com/2304-8158/14/15/2566<i>Staphylococcus aureus</i>pyruvate carboxylaseantimicrobial resistancebiofilmTCA cyclepurine metabolism |
| spellingShingle | Zifeng Mai Jiahui Li Zeqiang Zhan Xiaorong Tian Wanwan Hou Mu He Chunlei Shi Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> Foods <i>Staphylococcus aureus</i> pyruvate carboxylase antimicrobial resistance biofilm TCA cycle purine metabolism |
| title | Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> |
| title_full | Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> |
| title_fullStr | Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> |
| title_short | Metabolic Master Switch: Pyruvate Carboxylase Fuels Antimicrobial Resistance and Virulence in Foodborne <i>Staphylococcus aureus</i> |
| title_sort | metabolic master switch pyruvate carboxylase fuels antimicrobial resistance and virulence in foodborne i staphylococcus aureus i |
| topic | <i>Staphylococcus aureus</i> pyruvate carboxylase antimicrobial resistance biofilm TCA cycle purine metabolism |
| url | https://www.mdpi.com/2304-8158/14/15/2566 |
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