Antibacterial Potential of Honeybee Venom and Monascus purpureus Extracellular Metabolites Against Multidrug-Resistant Pathogenic Bacteria

Antimicrobial resistance (AMR) poses a critical global health threat, driving the search for alternative treatments to conventional antibiotics. In this study, the antibacterial properties of honeybee venom (BV) and fungal <i>Monascus purpureus</i> red dye (RD) were evaluated against three multidrug-resistant bacterial pathogens. Extracts of BV and RD exhibited dose-dependent antibacterial activity against the three tested bacteria, with their strongest effectiveness against <i>S. aureus</i> (minimum inhibitory concentrations [MIC] = 3.18 and 6.315 μg·mL^-1, respectively). Although the three bacterial strains were resistant to the antibiotic ampicillin-sulbactam (10/10 µg), both extracts exhibited superior antibacterial activity against the three bacterial strains compared to five standard antibiotics, especially RD extract, which produced the largest inhibition zone (20 ± 0.20 mm) against <i>S. aureus.</i> The larger inhibition zones against <i>S. aureus</i> suggest its high sensitivity, whereas <i>E. coli</i> and <i>E. faecalis</i> exhibited smaller inhibition zones, indicating less sensitivity to BV and RD extracts. Differences in the inhibition zones suggest the variations in antimicrobial activity between the two extracts and their strain-specific effectiveness. Scanning electron microscopy (SEM) revealed that BV and RD extracts disrupted the bacterial plasma membrane, suggesting that the bioactive compounds penetrate the bacterial cell wall and alter its integrity. Furthermore, GC-MS-based analysis revealed that the chemical composition of BV and RD extracts exhibited highly diverse structures, including complex polycyclic systems, porphyrins, steroids, and esters. For instance, 42 metabolites were identified in the BV extract, which mainly were organic and metal-organic compounds; however, only 23 molecules were identified in RD extract, which mainly were fatty acids and their derivatives. The diversity in the chemical compositions of both extracts highlights their potential applications in pharmaceuticals, materials, and biochemistry fields. Collectively, these findings indicate that honeybee venom and the red dye from <i>M. purpureus</i> have promising antibacterial properties and warrant further investigation as potential alternatives to conventional antibiotics. Further multi-ligand docking-based virtual screening studies are required to identify the most promising detected metabolite(s) within both BV and RD extracts.