Guttiferone E from Brazilian red propolis inhibited wound-isolated methicillin-resistant Staphylococcus aureus and...

Propolis has been traditionally used to treat inflammatory and infectious diseases, and it is still used and researched worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) may cause invasive infections and propolis anti-MRSA activity has been analyzed.

A standardized red propolis extract (SRPE), its benzophenones-rich fraction (BRF), and isolated benzophenones (guttiferone E - GUT E, and oblongifolin B - OBL B) were assayed for their antibacterial and immunomodulatory action.

Formulations (BRP28, BRP29, BRP150, BRP153, and BRPLUS) were prepared and their minimum inhibitory concentrations (MIC) were assessed. The synergistic action of GUT E with antimicrobials was evaluated on a wound-isolated MRSA, as well as the inhibition of biofilm formation by the formulations (BRP28 and BRP29) and GUT E. Tohoku Hospital Pediatrics-1 (THP-1) cells were used to investigate cytokine production and the bactericidal activity of suppressed macrophages against MRSA. Computational predictions were performed with GUT E and antimicrobials to observe their interaction with the active and allosteric site of penicillin-binding protein 2a (PBP2a).

SRPE and BRF were not efficient against MRSA while GUT E and OBL B exerted a potent activity. GUT E exerted a synergistic effect with carbapenems and vancomycin. BRP28, BRP29, and GUT E inhibited biofilm formation and increased the antibacterial capacity of suppressed macrophages, with no differences in cytokine production. GUT E showed a high binding affinity to PBP2a.

GUT E exhibited a direct anti-MRSA activity and indirectly enhanced the macrophage bactericidal activity. Molecular docking suggested that GUT E has a versatile interaction with PBP2a.