The emergence of antibiotic resistance necessitates not only the identification of new compounds with antimicrobial properties, but also new strategies and combination therapies to circumvent this growing problem. Here, we report synergistic activity against methicillin-resistant Staphylococcus aureus (MRSA) of the β-lactam antibiotic oxacillin combined with 7,8-dideoxygriseorhodin C in vitro. Ongoing efforts to identify antibiotics from marine mollusk-associated bacteria resulted in the isolation of 7,8-dideoxygriseorhodin C from a Streptomyces sp. strain cultivated from a marine gastropod tissue homogenate. Despite the long history of 7,8-dideoxygriseorhodin C in the literature, the absolute configuration has never been previously reported. A comparison of measured and calculated ECD spectra resolved the configuration of the spiroketal carbon C6, and 2D ROESY NMR spectroscopy established the absolute configuration as 6s,6aS. The compound is selective against Gram-positive bacteria including MRSA and Enterococcus faecium with an MIC range of 0.125-0.5 μg ml-1. Moreover, the compound synergizes with oxacillin against MRSA as observed in the antimicrobial microdilution and time-kill assays. Simultaneous treatment of the compound with oxacillin resulted in an approximately tenfold decrease in MIC with a combination index of <0.5, indicating synergistic anti-MRSA activity.

中文翻译：

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协同抗甲氧西林抗金黄色葡萄球菌（MRSA）活性和7,8-二甲氧基灰黄霉素C的绝对立体化学。

抗生素耐药性的出现不仅需要鉴定具有抗菌特性的新化合物，而且还需要新的策略和联合疗法来避免这一日益严重的问题。在这里，我们报告对β-内酰胺类抗生素奥沙西林与7,8-双脱氧griseorhodin C结合的耐甲氧西林金黄色葡萄球菌（MRSA）的协同活性。不断从海洋软体动物相关细菌中鉴定抗生素的努力导致从链霉菌属菌种中分离出7,8-二脱氧谷胱甘肽C。从海洋腹足动物组织匀浆培养的菌株。尽管在文献中7,8-二脱氧谷胱甘肽C的历史很长，但是绝对构型以前从未被报道过。通过比较测得的和计算出的ECD光谱，可以解析出螺碳C6的构型，2D ROESY NMR光谱确定的绝对构型为6s，6aS。该化合物对MIC范围为0.125-0.5μgml-1的革兰氏阳性细菌（包括MRSA和粪肠球菌）具有选择性。而且，如抗微生物微量稀释和时间杀灭试验所观察到的，该化合物与奥沙西林协同抗MRSA。用奥沙西林同时处理该化合物可导致MIC下降约10倍，且组合指数<0.5，表明协同的抗MRSA活性。如抗微生物微量稀释和时间杀灭试验所观察到的，该化合物与奥沙西林协同抗MRSA。用奥沙西林同时处理该化合物可导致MIC下降约10倍，且组合指数<0.5，表明协同的抗MRSA活性。如抗微生物微量稀释和时间杀灭试验所观察到的，该化合物与奥沙西林协同抗MRSA。用奥沙西林同时处理该化合物可导致MIC下降约10倍，且组合指数<0.5，表明协同的抗MRSA活性。