Vancomycin combined with Zhenqi Granule can inhibit Methicillin-Resistant Staphylococcus aureus more effectively than Vancomycin alone.

OBJECTIVE

Methicillin-resistant Staphylococcus aureus (MRSA) has developed increasing resistance to vancomycin (Van), especially in biofilm-associated infections. This study explores the combination of Van with Zhenqi Granule (ZQ), a traditional Chinese herbal formula with documented antimicrobial activity, as a potential strategy to overcome Van resistance.

METHODS

The minimum inhibitory concentration (MIC) and combined effects of Van and ZQ on planktonic MRSA were determined using checkerboard broth dilution and growth curves. Biofilm viability was assessed via colony counting and confocal microscopy. ELISA was used to measure biofilm matrix components (PIA, eDNA) and alkaline phosphatase (AKP) levels. Propidium iodide staining and transmission electron microscopy were applied to observe membrane permeability and cell wall ultrastructure. Gene expression of biofilm- and wall teichoic acid (WTA)-associated genes was quantified by RT-PCR.

RESULTS

The MICs of Van and ZQ were 1 μg/mL and 25 mg/mL, respectively. The combination of 1/2×MIC Van and 1/2×MIC ZQ completely inhibited planktonic MRSA growth over 24 h and significantly reduced biofilm viability. The levels of PIA, eDNA, and c-di-AMP in the biofilm matrix were notably decreased. ZQ increased extracellular AKP levels, enhanced membrane permeability, and induced plasmolysis. The combination also significantly downregulated the transcription of biofilm-related genes (icaA, purF) and WTA synthesis genes (tarH, fmtA, dltA).

CONCLUSION

Van combined with ZQ effectively inhibits MRSA growth in both planktonic and biofilm states. The synergistic mechanism involves ZQ-induced disruption of cell wall integrity, which enhances the antibacterial effect of Van against MRSA biofilms, providing a potential strategy for combined therapy against MRSA infections.