The antimicrobial properties of numerous natural compounds extracted from various plants are being extensively investigated, accompanied by the growing interest in using plant constituents as drugs or antimicrobial agents (Berida et al., 2024). Given that the potential health risks and safety concerns about synthetic food additives frequently cause anxiety among consumers, such natural antimicrobials present promising alternatives to chemical antimicrobials in food preservation (El-Saber Batiha et al., 2021; Giaouris et al., 2014). Hence, exploring the effective natural plant-derived antimicrobials for controlling foodborne pathogenic bacteria is of great importance, which plays a fundamental role in extending the shelf-life of meat and ensuring consumers' safety.

Current studies have confirmed that natural antimicrobial components, especially plant-derived antimicrobials, exhibited enormous application potential in inhibiting food spoilage, maintaining their quality stability, and extending their shelf-life (Wang et al., 2024; Gao et al., 2024). Among diverse plant-derived compounds, resveratrol is garnering great attention due to its multifaceted biological activities. Resveratrol is a non-flavonoid polyphenolic compound, scientifically known as 3,4′,5-trihydroxystilbene (C12H14O3), which is widely found in more than 70 plants, such as grapes, peanuts, and Polygonum cuspidatum (Zhang et al., 2021). As a plant antitoxin, resveratrol is produced when plants are exposed to fungal infections or other environmental stresses (Arias et al., 2024). It was reported that resveratrol has various biological functions, including antioxidant and antimicrobial activities, anti-tumor, and immune regulation (Yang et al., 2025b). To data, the antimicrobial ability of resveratrol is targeted at inhibiting some special foodborne pathogens (e.g., Salmonella typhimurium; Escherichia coli, E. coli) by reducing their swimming motility and chemotactic ability (Lou et al., 2023; Ruan et al., 2021). Despite the antimicrobial properties of resveratrol are known, its bacteriostatic efficacy against MRSA in complex meat matrices still remains underexplored. This critical gap hinders its practical application in meat preservation and the targeted control of foodborne MRSA. Therefore, further research is needed to evaluate its efficacy in complex meat matrices and to elucidate its antimicrobial mechanisms.

Among the top foodborne pathogens, Staphylococcus aureus (S. aureus) is a Gram-positive bacterium that can cause food poisoning globally, especially for animal-derived foods (Somda et al., 2024). Indeed, Ikuta et al. (2022) stated that S. aureus caused more patient deaths (more than 1 million deaths) and years of life lost (34.3 million) compared to other pathogenic bacteria, such as Klebsiella pneumoniae, E. coli, and Pseudomonas aeruginosa. Methicillin-resistant Staphylococcus aureus (MRSA) is a special type of S. aureus with penicillin-binding protein 2a (PBP2a, encoded by the mecA gene) and has low affinity for β-lactam antimicrobials, allowing MRSA to show resistance to antibiotics (Yehia et al., 2020). MRSA is less prevalent than methicillin-sensitive S. aureus, but it is more pathogenic as well as antimicrobial resistant (Nascimento et al., 2025; Roy et al., 2024). As a dangerous opportunistic pathogen, MRSA infection can lead to various clinical problems, including endocarditis and pneumonia (Liu et al., 2023). It is speculated that resveratrol may also have an inhibitory effect on MRSA growth. However, little detailed information is available about the resveratrol inhibition of MRSA, as well as its antimicrobial mechanism against MRSA. Proteomics is an emerging biological technique that characterizes changes in intracellular protein expression and the related metabolic pathways, which has been widely used to elucidate the complex inner antimicrobial mechanisms of various antimicrobial actions (Zhang et al., 2020). However, to our knowledge, few have reported the antimicrobial mechanism of resveratrol by focusing on proteomic changes in the MRSA associated with foodborne contexts.

In this study, the inhibitory efficacy of resveratrol on the MRSA growth in beef under two storage conditions (4 °C for 7 days and 25 °C for 3 days) and its antimicrobial mechanism involving its disruptive effects on cellular structures (cell wall and membrane) were systematically investigated. Furthermore, Tandem Mass Tag (TMT) quantitative proteomics was employed to identify the differentially expressed proteins and their functions after the resveratrol treatment. Our findings will provide fundamental insights and experimental evidence to support the development of resveratrol as a natural antimicrobial agent for controlling foodborne MRSA.