Synergistic Anti-bacterial Effects of Phellinus baumii Ethyl Acetate Extracts and β-Lactam Antimicrobial Agents Against Methicillin-Resistant Staphylococcus aureus.

Abstract

BackgroundThe development of new drugs or alternative therapies effective against methicillin-resistant Staphylococcus aureus (MRSA) is of great importance, and various natural anti-MRSA products are good candidates for combination therapies. We evaluated the antibacterial activities of a Phellinus baumii ethyl acetate extract (PBEAE) and its synergistic effects with β-lactams against MRSA.MethodsThe broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the PBEAE. The PBEAE synergistic effects were determined by evaluating the MICs of anti-staphylococcal antibiotic mixtures, with or without PBEAE. Anti-MRSA synergistic bactericidal effects of the PBEAE and β-lactams were assessed by time-killing assay. An ELISA was used to determine the effect of the PBEAE on penicillin binding protein (PBP)2a production.ResultsThe MICs and MBCs of PBEAE against MRSA were 256-512 and 1,024-2,048 µg/mL, respectively. The PBEAE significantly reduced MICs of all β-lactams tested, including oxacillin, cefazolin, cefepime, and penicillin. However, the PBEAE had little or no effect on the activity of non-β-lactams. Time-killing assays showed that the synergistic effects of two β-lactams (oxacillin and cefazolin) with the PBEAE were bactericidal in nature (Δlog10 colony forming unit/mL at 24 hr: 2.34-2.87 and 2.10-3.04, respectively). The PBEAE induced a dose-dependent decrease in PBP2a production by MRSA, suggesting that the inhibition of PBP2a production was a major synergistic mechanism between the β-lactams and the PBEAE.ConclusionsPBEAE can enhance the efficacy of β-lactams for combined therapy in patients infected with MRSA.