Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4–512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis. At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G. Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.

抗生素与天然产物的结合是增强抗生素活性和克服抗生素耐药性的有前途的策略。本研究的目的是研究桑属中的戊烯醛化酚醛固醇和桑rus蛋白是否具有增强金黄色葡萄球菌和表皮葡萄球菌的抗生素活性并逆转其耐药性的能力。。选择常用的抗生素（奥沙西林，红霉素，庆大霉素，环丙沙星，四环素，克林霉素）进行联合研究。棋盘格法和时间杀灭法分别用于研究莫鲁生或kuwanon G与抗生素之间潜在的抑菌和杀菌协同作用。根据分数抑制浓度指数和响应面模型，共鉴定出二十种具有抑菌协同作用的组合（14种莫鲁辛-抗生素组合，6个kuwanon G-抗生素组合），且其最低抑菌浓度值降低了4-512倍。组合。morusin和kuwanon G均可逆转耐甲氧西林的金黄色葡萄球菌的奥沙西林耐药性。另外，莫鲁辛逆转了表皮葡萄球菌的四环素抗性。在最低抑菌浓度的一半时，莫鲁辛与奥沙西林或庆大霉素的组合显示对耐甲氧西林的金黄色葡萄球菌具有杀菌协同作用。荧光和微分干涉对比显微镜和扫描电子显微镜显示，在暴露于morusin或kuwanon G的耐甲氧西林的金黄色葡萄球菌中，膜通透性增加，细胞内物质大量泄漏。总体而言，我们的发现强烈表明，两种烯丙基化的化合物都是开发新型抗菌联合疗法的良好候选者。