Caffeic Acid Phenethyl Ester from NanoPropolis Inhibits Peptide Deformylase in Staphylococcus aureus and Pseudomonas aeruginosa: A Novel Strategy Against Endocarditis

Bacterial infections, particularly bacteremia and bacterial endocarditis caused by Staphylococcus aureus and Pseudomonas aeruginosa, pose significant global health challenges. Peptide Deformylase (PDF), a metalloenzyme essential for bacterial viability and absent in eukaryotic cells, is a promising target for novel antibacterial drug development. Caffeic Acid Phenethyl Ester (CAPE), a major active component of propolis, exhibits potent antimicrobial properties. This study investigates the potential of nanoencapsulated CAPE derived from Apis trigona propolis as a therapeutic agent against S. aureus and P. aeruginosa by inhibiting bacterial PDF activity. Physicochemical characterization confirmed the successful formation of stable nanoencapsulates with an average particle size of 109 ± 15 nm and good colloidal stability. Molecular docking studies revealed that CAPE exhibits strong binding affinity to the active sites of S. aureus PDF (PDB ID: 1Q1Y) and P. aeruginosa PDF (PDB ID: 1LRY), comparable to or exceeding that of the reference inhibitor, actinonin. Detailed analysis of docking poses indicated crucial interactions with key amino acid residues within the PDF active site. Furthermore, 20 ns molecular dynamics simulations demonstrated that the CAPE-PDF complexes remained stable, maintaining key hydrogen bonds and hydrophobic interactions, indicating robust and persistent binding. These findings suggest that nanoencapsulated CAPE holds significant promise as a novel antibacterial strategy by targeting essential bacterial PDF activity, potentially mitigating the risk of severe systemic infections like bacterial endocarditis.