Tannic Acid Targets Small Protein B to Regulate Biofilms and Ameliorate Multi‑Organ Injury in a Murine Model of Methicillin-resistant Staphylococcus aureus‑induced Sepsis

Methicillin-resistant Staphylococcus aureus (MRSA)-induced sepsis poses clinical challenges due to multidrug resistance. Tannic acid (TA), a natural polyphenol, is a potential antibacterial agent; however, its core anti-MRSA targets and molecular mechanisms remain unclear. Small protein B (SmpB), a key regulator of the bacterial trans-translation system, contributes to biofilm formation, virulence expression, and stress adaptation. Therefore, this study aimed to elucidate the mechanism through which TA targets SmpB for MRSA inhibition. In vitro, TA significantly reduced MRSA biofilm biomass with an 81.65% inhibition rate at 1/2 minimum inhibitory concentration and disrupted its structural integrity. Through proteomics, protein–protein interaction analysis and molecular docking with a binding free energy of -6.971 kcal·mol⁻¹, SmpB may have been the core target of TA. The MRSA USA300 deletion strain (ΔsmpB) showed significantly reduced biofilm formation, impaired structural integrity and decreased extracellular matrix synthesis, while the complemented strain restored these phenotypes (p < 0.01). In a murine sepsis model, tannic acid alleviated pathological injury in the lung, liver, and kidney, and downregulated the transcriptional and protein levels of inflammatory factors interleukin 1β and 6, tumor necrosis factor α and procalcitonin. Mice infected with ΔsmpB had milder organ damage and lower inflammation than wild-type-infected mice, and TA treatment in ΔsmpB-infected mice achieved superior therapeutic effects. This study demonstrated that TA exerts anti-MRSA activity through modulating SmpB to inhibit biofilm formation and elucidated its mechanism of action.