Synergistic effects of mupirocin and an isoflavanone isolated from Erythrina variegata on growth and recovery of methicillin-resistant Staphylococcus aureus

The phytochemical 2',4-dihydroxy-8- gamma,-gamma-dimethylallyl-2",2"-dimethylpyrano[5",6":6,7]isoflavanone (bidwillon B) was isolated from Erythrina variegata and its antibacterial properties against methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Bidwillon B inhibited the growth of 12 MRSA strains at minimum inhibitory concentrations (MICs) of 3.13-6.25 mg/l, while MICs of mupirocin were 0.20-3.13 mg/l. The minimum bactericidal concentration (MBC) for bidwillon B and mupirocin against MRSA were 6.25-25 mg/l (MBC90: 12.5 mg/l) and 3.13-25 mg/l (MBC90: 25 mg/l), respectively. When bidwillon B and mupirocin were combined, synergistic effects were observed for I I strains of MRSA (fractional inhibitory concentration indices, 0.5-0.75). The MBCs of mupirocin in the presence of bidwillon B (3.13 mg/l) were reduced to 0.05-1.56 mg/l. Bidwillon B at MIC values strongly inhibited incorporation of radio-labelled thymidine, uridine, glucose and isoleucine into MRSA cells. Mupirocin showed lower inhibitory effects than bidwillon B on thymidine, uridine and glucose incorporation, but incorporation of isoleucine was completely blocked with this antibiotic. These results indicate that bidwillon B possesses sufficient anti-MRSA activity for inhibiting growth and recovery, and that the compound acts synergistically with mupirocin. The results also suggest that both compounds act on MRSA via different mechanisms. Bidwillon B may prove to be a potent phytotherapeutic and/or combination agent with mupirocin in the elimination of nasal and skin carriage of MRSA. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.