Citric Acid Controls the Activity of YopH Bacterial Tyrosine Phosphatase

Drug Des Devel Ther. 2024 Apr 11:18:1165-1174. doi: 10.2147/DDDT.S444500. eCollection 2024.

Abstract

Purpose: Citric acid (CA) is a tricarboxylic acid with antioxidant and antimicrobial properties. Based on previous studies, the small compound with its three carboxylic groups can be considered a protein tyrosine phosphatase inhibitor. YopH, a protein tyrosine phosphatase, is an essential virulence factor in Yersinia bacteria.

Materials and methods: We performed enzymatic activity assays of YopH phosphatase after treatment with citric acid in comparison with the inhibitory compound trimesic acid, which has a similar structure. We also measured the cytotoxicity of these compounds in Jurkat T E6.1 and macrophage J774.2 cell lines. We performed molecular docking analysis of the binding of citric acid molecules to YopH phosphatase.

Results: Citric acid and trimesic acid reversibly reduced the activity of YopH enzyme and decreased the viability of Jurkat and macrophage cell lines. Importantly, these two compounds showed greater inhibitory properties against bacterial YopH activity than against human CD45 phosphatase activity. Molecular docking simulations confirmed that citric acid could bind to YopH phosphatase.

Conclusion: Citric acid, a known antioxidant, can be considered an inhibitor of bacterial phosphatases.

Keywords: CD45 phosphatase; Yersinia; YopH; bacterial virulence factors; citric acid; protein tyrosine phosphatase; trimesic acid.

MeSH terms

  • Antioxidants*
  • Humans
  • Molecular Docking Simulation
  • Protein Tyrosine Phosphatases* / chemistry
  • Protein Tyrosine Phosphatases* / metabolism
  • Tricarboxylic Acids*
  • Tyrosine

Substances

  • trimesic acid
  • Antioxidants
  • Protein Tyrosine Phosphatases
  • Tyrosine
  • Tricarboxylic Acids

Grants and funding

This research was funded by IDUB Program’s Research Project for Young Scientists MTN No. 71-1215 (Medical University of Gdansk, Poland).