Natural Strategies against Superbugs: Anti-Virulence Effects of Stingless Bee Propolis on Clinical MRSA Isolates

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major public health concern due to its resistance to β-lactam antibiotics and its ability to cause persistent infections. As antibiotic resistance excalates, natural products derived from functional foods offer promising alternatives. Stingless bee propolis, a resinous compound collected by bees from plant exudates, known for its nutritional and medicinal properties, is gaining interest for its inhibitory effects against bacteria. However, its role in targeting bacterial virulence factors remains largely unexplored. This study investigated the anti-virulence effects of stingless bee propolis against clinical MRSA isolates. Following confirmation of methicillin resistance through antibiotic susceptibility testing, hydroethanolic extraction of propolis was performed. The sub-inhibitory concentration (SIC) of the extract was determined to be 1.563% (w/v) via broth microdilution. At this concentration, propolis treatment led to a reduction in β-lactamase activity (6.86–19.42%), suggesting interference with resistance mechanisms. Phenotypic assays further demonstrated significant reductions in several key virulence traits, including protease activity (66.67–100%), haemolysin production (8.50–31.20%), nuclease activity (13.99–23.42%), surfactant production (12.86–57.14%), colony spreading (20.88–65.72%), and biofilm formation (38.42–77.17%). In addition, scanning electron microscopy (SEM) revealed distinct morphological alterations in propolis-treated MRSA cells, indicating structural disruption likely linked to the attenuation of virulence. These cellular changes support the hypothesis that propolis affects bacterial function without directly killing the bacteria. These findings highlight that stingless bee propolis, a functional food-derived substance, can disrupt multiple pathogenic mechanisms of MRSA without exerting direct bactericidal pressure. This natural compound may serve as an adjunctive therapy, reducing infection severity through the modulation of virulence, while helping preserve antibiotic efficacy. This study underscores the potential of functional food products in medical applications, bridging the gap between nutrition and therapeutics, offering a novel strategy for managing antimicrobial resistance.