Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus
Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus
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DOI：
10.5455/jice.20160906035020
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Viswanathan, Vinodhini
中科院分区：
文献类型：
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作者：
Ekambaram, Sanmuga Priya;Perumal, Senthamil Selvan;Viswanathan, Vinodhini
目的/背景：药用植物通过合成酚类等次生代谢物来抵抗微生物。迷迭香酸(RA)是一种广泛存在于植物体内的苯丙烷类化合物，是著名的治疗和美容剂。耐甲氧西林金黄色葡萄球菌(MRSA)对各种β-内酰胺类抗生素耐药，甚至对最有效的抗生素也构成威胁。为提高抗生素对多重耐药菌的抗菌效果，减少抗生素用量，研究了维甲酸与标准抗生素对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的抗菌活性及协同作用。材料和方法：采用琼脂扩散法检测维甲酸对金黄色葡萄球菌和临床分离的耐甲氧西林金黄色葡萄球菌的抗菌活性。用肉汤稀释法测定RA的最小抑菌浓度(MIC)。采用肉汤棋盘法和时间杀灭动力学法研究RA与不同抗生素对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的协同作用。采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法研究了维甲酸对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌黏附基质分子识别能力的影响。结果：RA对金黄色葡萄球菌的MIC为0.8 mg/ml，对MRSA的MIC为10 mg/ml。RA与万古霉素、氧氟沙星、阿莫西林对金黄色葡萄球菌有协同作用，对MRSA仅与万古霉素有协同作用。时间-杀灭分析表明，协同作用比单独使用抗生素更有效。维甲酸联合万古霉素对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌MSCRAMM的蛋白表达有明显的抑制作用，而不是单独作用。结论：维甲酸与抗生素对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌有协同作用。RA对MSCRAMM的表面蛋白有抑制作用，尽管RA与抗生素有协同作用，但MIC较高。因此，进一步研究提高RA的疗效可以将其发展为抗生素的佐剂。
Aim/Background: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of beta-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics against S. aureus and MRSA was investigated. Materials and Methods: Antibacterial activity of RA against S. aureus and a clinical isolate of MRSA was evaluated by agar well diffusion method. Minimum inhibitory concentration (MIC) of RA was determined by broth dilution method. Synergism of RA with various antibiotics against S. aureus and MRSA was studied by broth checkerboard method and time-kill kinetic assay. Effect of RA on microbial surface components recognizing adhesive matrix molecules (MSCRAMM's) of S. aureus and MRSA was studied using sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Results: MIC of RA was found to be 0.8 and 10 mg/ml against S. aureus and MRSA, respectively. RA was synergistic with vancomycin, ofloxacin, and amoxicillin against S. aureus and only with vancomycin against MRSA. The time-kill analysis revealed that synergistic combinations were a more effective than individual antibiotics. MSCRAMM's protein expression of S. aureus and MRSA was markedly suppressed by RA + vancomycin combination rather than RA alone. Conclusion: The synergistic effects of RA with antibiotics were observed against S. aureus and MRSA. RA showed inhibitory effect on the surface proteins MSCRAMM's. Even though RA was shown to exhibit a synergistic effect with antibiotics, the MIC was found to be higher. Thus, further studies on increasing the efficacy of RA can develop it as an adjuvant for antibiotics.