Synergistic antibacterial activity of benzyl isothiocyanate and resveratrol against Staphylococcus aureus: Multi-omics perspective insights on cell wall disruption

Staphylococcus aureus ( S. aureus ) is a typical foodborne pathogen, and the development of novel synergistic antimicrobial strategies is urgently needed. Therefore, the aim of this study was to investigate the mechanism underlying the synergistic inhibition of S. aureus by benzyl isothiocyanate (BITC) and resveratrol (RES). The synergistic effect of BITC and RES on S. aureus was verified by a time-elimination curve, cell hemolysis, intracellular reactive oxygen species accumulation and transmission electron microscopy. The results of the transcriptomic and proteomic analyses revealed that the combination of BITC and RES against S. aureus synergistically downregulated the expression of the cell wall anchoring protein immunoglobulin G-binding protein (Sbi) compared with that in the individual treatments, a finding further supported by qRT-PCR and molecular docking. In addition, synergistic effects significantly disrupted cell wall integrity, alkaline phosphatase leakage increased by 1.1–1.9 times, the zeta potential increased by 3.0–6.3 mV, and the hydrophobicity decreased by 19.2 %–25.0 %. These findings uncover a novel mechanism of synergistic antimicrobial action and provide valuable clues for developing strategies against S. aureus . • Benzyl isothiocyanate (BITC) combined resveratrol (RES) inhibited S. aureus . • BITC and RES demonstrated synergistic effect on several sbi -related genes. • BITC and RES had synergistic effect on cell wall-related functions. • BITC and RES may synergistically inhibit bacteria by targeting the Sbi protein.