Combinatorial Activity of Flavonoids with Antibiotics Against Drug-Resistant Staphylococcus aureus
Combinatorial Activity of Flavonoids with Antibiotics Against Drug-Resistant Staphylococcus aureus
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DOI：
10.1089/mdr.2014.0252
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发表时间：
2015-12-01
影响因子：
2.6
通讯作者：
Simoes, Manuel
中科院分区：
文献类型：
--
作者：
Abreu, Ana Cristina;Serra, Sofia C.;Simoes, Manuel
在抗生素耐药性日益增加的情况下，使用抗药性改良剂是一种潜在的策略，用于延长抗生素的有效寿命。由于某些黄酮类化合物是有效的细菌外排泵抑制剂，我们评估了桑色素、芦丁、栎素、橙皮苷和(+)-儿茶素与抗生素环丙沙星、四环素、红霉素、苯唑西林和氨苄西林对耐药金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌)的联合活性。四种已建立的方法被用来确定每种组合的联合有效性：微量稀释法、计时杀伤法、Etest法和双纸片扩散法。此外，还在小鼠成纤维细胞系中评价了黄酮类化合物的细胞毒性。对某些金黄色葡萄球菌的最低抑菌浓度为环丙沙星、四环素和红霉素的3-16倍。芦丁、橙皮苷和(+)-儿茶素没有促进抗生素的任何增强作用。尽管这些植物化学物质在高浓度下具有潜在的细胞毒性(成纤维细胞的IC50分别为41.8 mg/L和67.5 mg/L)，但通常用于多种治疗目的的补充剂。除时间杀灭试验外，所有方法均表现出高度的一致性，没有任何明显的菌株特异性。
The use of resistance-modifying agents is a potential strategy that is used to prolong the effective life of antibiotics in the face of increasing antibiotic resistance. Since certain flavonoids are potent bacterial efflux pump inhibitors, we assessed morin, rutin, quercetin, hesperidin, and (+)-catechin for their combined activity with the antibiotics ciprofloxacin, tetracycline, erythromycin, oxacillin, and ampicillin against drug-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus. Four established methods were used to determine the combined efficacy of each combination: microdilution checkerboard assays, time-kill determinations, the Etest, and dual disc-diffusion methods. The cytotoxicity of the flavonoids was additionally evaluated in a mouse fibroblast cell line. Quercetin and its isomer morin decreased by 3- to 16-fold the minimal inhibitory concentration of ciprofloxacin, tetracycline, and erythromycin against some S. aureus strains. Rutin, hesperidin, and (+)-catechin did not promote any potentiation of antibiotics. Despite the potential cytotoxicity of these phytochemicals at a high concentration (fibroblast IC50 of 41.8 and 67.5mg/L, respectively), quercetin is commonly used as a supplement for several therapeutic purposes. All the methods, with exception of the time-kill assay, presented a high degree of congruence without any apparent strain specificity.