The β-lactam ticarcillin is a Staphylococcus aureus UDP-N-acetylglucosamine 2-epimerase binder

Area of Science:

• Microbiology
• Drug Discovery
• Computational Chemistry

Background:

• Infectious diseases cause 25% of global deaths, with rising antibiotic resistance exacerbating the threat.
• Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), is a major cause of healthcare-associated infections.

Purpose of the Study:

• To identify potential weak binders of Staphylococcus aureus UDP-N-acetylglucosamine 2-epimerase.
• To investigate the binding mode and stability of identified ligands.

Main Methods:

• Utilized docking screening to identify potential ligands.
• Employed isothermal analysis of differential scanning fluorimetry to validate ligand binding.
• Performed equilibrium molecular dynamics (MD) simulations to confirm binding pose and stability.

Main Results:

• Ticarcillin was identified as a weak binder of S. aureus UDP-N-acetylglucosamine 2-epimerase.
• Isothermal analysis confirmed ticarcillin's interaction with the enzyme.
• MD simulations validated the docking binding mode, showing a stable pose with significant binding energy contributions from specific amino acid-ligand interactions.

Conclusions:

• Ticarcillin shows weak binding to S. aureus UDP-N-acetylglucosamine 2-epimerase.
• The identified binding interactions provide a basis for further drug development efforts against resistant S. aureus strains.