Synergistic Antibacterial Effect and Antibacterial Action Mode of Chitosan-Ferulic Acid Conjugate against Methicillin-Resistant Staphylococcus aureus.

We evaluated the synergistic antibacterial effect in combination with the chitosan-ferulic acid conjugate (CFA) and β-lactam antibiotics, such as ampicillin, penicillin, and oxacillin, against methicillin-resistant Staphylococcus aureus (MRSA) using fractional inhibitory concentration (FIC) indices. CFA clearly reversed the antibacterial activity of ampicillin, penicillin, and oxacillin against MRSA in the combination mode. Among these antibiotics, the combination of oxacillin-CFA resulted in a ∑FICmin range of 0.250 and ∑FICmax of 0.563, suggesting that the oxacillin-CFA combination resulted in an antibacterial synergy effect against MRSA. In addition, we determined that CFA inhibited the mRNA expression of gene mecA and the production of PBP2a, which is a key determinant for β-lactam antibiotic resistance, in a dosedependent manner. Thus, the results obtained in this study supported the idea on the antibacterial action mechanism that oxacillin will restore the antibacterial activity against MRSA through the suppression of PBP2a production by CFA.