School of Pharmacy, Fudan University, 826 Zhangheng Road, Zhangjiang, Shanghai 201203, China.
School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.
Int J Antimicrob Agents. 2020 Sep;56(3):106098. doi: 10.1016/j.ijantimicag.2020.106098. Epub 2020 Jul 21.
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.
金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌(MRSA))仍然是医院和社区环境中的一个挑战。设计和发现新的化合物来应对耐药菌已成为当今抗感染研究最重要的领域之一。本研究旨在通过从中药中寻找非 MRSA 外排机制底物且通过其他尚未描述的机制克服细菌耐药性的协同天然抗菌产品来解决 MRSA 问题。使用标准棋盘法测定体外协同活性,并通过溴化乙锭外排测定法进行机制研究。通过体内实验,在菌血症小鼠模型中比较了不同浓度组合的疗效。天然产物槐属黄酮 G 表现出体外和体内特异性协同抗菌作用,可作为具有抗生素增效活性的药物的模板,用于治疗金黄色葡萄球菌(包括 MRSA)引起的感染。