Antibacterial potential of hippophaenin-A against foodborne pathogens: a comprehensive in silico study

Bacteria are a major cause of foodborne illnesses. Natural compounds with antimicrobial properties, such as tannins, can inhibit bacterial growth and enhance food safety. Peptidoglycan, a key component of the bacterial cell wall, is essential for bacterial growth, making penicillin-binding proteins (PBPs) in its peptidoglycan synthesis pathway a promising target for antibacterial strategies. Hippophaenin-A, a tannin from Hippophae rhamnoides L. (sea buckthorn), was analyzed through computer simulations to investigate its inhibitory effects on eight PBPs from Staphylococcus aureus , Bacillus cereus , Escherichia coli , and Salmonella typhimurium . Phylogenetic analysis of PBP sequences was conducted using MEGA 11.0. 3D models of PBPs were obtained from the AlphaFold2 Protein Structure Database and validated. Molecular docking with AutoDock Vina assessed the binding affinity and interactions of hippophaenin-A and chloramphenicol in PBP active sites. Molecular dynamics simulations (50 ns) were performed for top docking complexes and native PBPs of foodborne pathogens. Physicochemical, pharmacokinetic, and toxicity (ADME/T) properties of hippophaenin-A were also evaluated. Hippophaenin-A e binding affinities of -9.4, and − 9.3 kcal/mol with the transpeptidase and transglycosylase catalytic sites of Salmonella typhimurium PBP1B, and Bacillus cereus PBP3, respectively, surpassing the positive control. These findings suggest its antibacterial activity may result from PBP inhibition. Additionally, it displayed favorable physicochemical and ADME properties, with toxicity predictions indicating no safety concerns for consumers. Further studies on hippophaenin-A could provide valuable insights for developing it as a natural antibacterial agent for food preservation.