Bactericidal effect of citronellal and molecular docking with KPC-2 of Klebsiella pneumoniae and PBP2A of Staphylococcus aureus

Infectious diseases remain a leading cause of death worldwide. Due to selective pressure, resistant bacteria, especially Klebsiella pneumoniae and Staphylococcus aureus, are frequently selected and disseminated in various environments. This study aimed to evaluate the antibacterial activity of citronellal against K. pneumoniae and S. aureus, as well as its interactions with enzymes associated with resistance to carbapenems and methicillin, KPC-2 and PBP2a, respectively. Bioassays were conducted to determine the minimum inhibitory and bactericidal concentrations. Rigid molecular docking assays were performed with fixed amino acid residues of KPC-2 and PBP2a, while the ligand was flexible. Citronellal inhibited bacterial growth and showed bactericidal activity against K. pneumoniae at 128 µg/mL and S. aureus at 64 µg/mL. Additionally, citronellal interacted with the active sites of KPC-2 and PBP2a, with binding energies of −4.30 and −4.05 kcal/mol, respectively. In conclusion, citronellal demonstrated bactericidal effects against the tested strains. However, despite its affinity for the target enzymes, the binding activity was lower compared to avibactam and penicillin G in the docking simulations.