Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), remains a challenge in hospital and community settings. The design and discovery of new compounds to deal with resistant bacteria has become one of the most important areas of anti-infective research today. The aim of this study was to address the problem of MRSA by searching for synergistic natural antibacterial products from traditional Chinese herbs that are not substrates for the efflux mechanisms of MRSA and that overcome bacterial drug resistance by other, as yet undescribed, mechanisms. In vitro synergistic activity was determined using the standard chequerboard method, and mechanistic studies were performed by an ethidium bromide efflux assay. Using in vivo experiments, the efficacies of different concentrations of the combinations were compared in a murine model of pyaemia. The natural product sophoraflavanone G showed specific synergistic antibacterial effects both in vitro and in vivo and may serve as a template for agents with antibiotic-potentiating activity for use against infections caused by S. aureus, including MRSA.
Keywords: Efflux pump; In vitro; In vivo; Norfloxacin; Sophoraflavanone G; Synergism.
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