Natural Products Laboratory, Institute of Biology, Leiden University, Leiden, The Netherlands.
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465, Porto, Portugal.
Sci Rep. 2017 Jun 19;7(1):3777. doi: 10.1038/s41598-017-03716-7.
The spread of multidrug-resistant Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA), has shortened the useful life of anti-staphylococcal drugs enormously. Two approaches can be followed to address this problem: screening various sources for new leads for antibiotics or finding ways to disable the resistance mechanisms to existing antibiotics. Plants are resistant to most microorganisms, but despite extensive efforts to identify metabolites that are responsible for this resistance, no substantial progress has been made. Plants possibly use multiple strategies to deal with microorganisms that evolved over time. For this reason, we searched for plants that could potentiate the effects of known antibiotics. From 29 plant species tested, Cytisus striatus clearly showed such an activity and an NMR-based metabolomics study allowed the identification of compounds from the plant extracts that could act as antibiotic adjuvants. Isoflavonoids were found to potentiate the effect of ciprofloxacin and erythromycin against MRSA strains. For the structure-activity relationship (SAR), 22 isoflavonoids were assessed as antibiotic adjuvants. This study reveals a clear synergy between isoflavonoids and the tested antibiotics, showing their great potential for applications in the clinical therapy of infections with antibiotic-resistant microorganisms such as MRSA.
耐多药金黄色葡萄球菌菌株（包括耐甲氧西林金黄色葡萄球菌，MRSA）的传播极大地缩短了抗葡萄球菌药物的有效寿命。为了解决这个问题，可以采取两种方法：从各种来源筛选新的抗生素先导物，或寻找方法使现有抗生素的耐药机制失活。植物对大多数微生物具有抗性，但尽管为确定负责这种抗性的代谢物进行了广泛的努力，但没有取得实质性进展。植物可能使用多种策略来应对随时间进化的微生物。出于这个原因，我们寻找可以增强已知抗生素效果的植物。在测试的 29 种植物中，金雀异黄素明显表现出这种活性，基于 NMR 的代谢组学研究鉴定了来自植物提取物的化合物，这些化合物可以作为抗生素佐剂发挥作用。异黄酮被发现可以增强环丙沙星和红霉素对 MRSA 菌株的作用。为了进行构效关系（SAR）研究，评估了 22 种异黄酮作为抗生素佐剂。这项研究揭示了异黄酮与测试抗生素之间的明显协同作用，表明它们在应用于治疗耐抗生素微生物（如 MRSA）感染的临床治疗方面具有巨大潜力。
