AIM Methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as one of the most important pathogens, which is endemic in hospitals worldwide.APS (dihydromyricetin) which has been extracted from Ampelopsis grossedentata (Hand-Mazz) W.T.Wang from Guangxi had been reported antibacterial activity against MSSA and MRSA in vitro and in vivo.The purpose of our study was to investigate the effects and underlying mechanisms of APS alone and in combination with β-1actam antibiotics on MRSA.METHODS Kirby-Bauer and mecA gene test were used to identify 15 MRSA strains isolated from hospital.The MICs of 4 MRSA strains including MSAR-6, MRSA-8, MRSA-9, MRSA-12 and the methicillin-susceptible Staphylococcus.aureus(MSSA) were tested by agar dilution method.The synergistic effects of APS with 6 β-lactam antibiotics against MRSA-6 were measured by checkerboard method with Fractional inhibitory concentration index (FICI).To evaluate the protective effect of APS alone and in combination with β-lactam antibiotics in vivo, MRSA abdominal infection and lung infection mice models were performed with intraperitoneal injection and intranasal inhalation of MRSA-6, respectively.Scanning and transmission electron microscopy were used to observe the ultrastructure of bacterial morphology treating with different concentrate APS alone and in combination with β-lactam antibiotics against MSSA and MRSA.RESULTS 4 strain MRSAs were identified with Kirby-Bauer and mecA gene test.The MICs of APS alone were 125 mg· L-1.Synergistic effect of APS and 5 β-lactam antibiotics such as penicillin, oxacillin, cefazolin, tienam, cefoxitin were detected with checkerboard-method to MRSA in vitro except cefepime which showed the additive effect with APS.APS in combination with tienam and cefoxitin can increase the survival rates of abdominal infected mice by MRSA, ED50 was 3.03 mg· kg-1 and 13.79 mg·kg-1 respectively, decreased 12 and 16.7 times than of tienam and cefoxitin alone.High dose APS in combination with tienam and cefoxitin also decreased the bacterial growth counting of lung of infected mice (P < 0.01 and P < 0.05), improved the inflammation of lung.The changes of morphology of MRSA were observed with scanning and transmission electron microscopy.Most cells wall of MRSA and MSSA were destroyed, the permeability of plasma membrane were changed and cytoplasmic contents of the cells leaking out.CONCLUSION APS has synergistic antibacterial effect with β-lactam antibiotics against MRSA in intro and in vivo.The mechanism of it may due to the breakage of bacteria cell wall.