Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, La Jolla, CA, USA.
J Antibiot (Tokyo). 2010 May;63(5):219-24. doi: 10.1038/ja.2010.22. Epub 2010 Mar 26.
The alarming rise of hospital- and community-associated methicillin-resistant Staphylococcus aureus (HA- and CA-MRSA) infections has prompted a desperate search for novel antibiotics. We discovered the streptogramin etamycin produced by an actinomycete species isolated from the coast of Fiji, the first time this antibiotic has been identified from a marine microbe. Etamycin was extracted and purified from this strain (CNS-575) and identified as a three-rotamer species by 2D NMR spectroscopy. Etamycin demonstrated potent activity against HA- and CA-MRSA in microbroth dilution assays, with minimum inhibitory concentrations (MIC) as low as 1-2 mg l(-1) against HA- and CA-MRSA strains. Furthermore, etamycin was also active against other Gram-positive and several Gram-negative pathogens and was found to be non-cytotoxic at concentrations more than 20-fold above MIC. Etamycin displayed favorable time-kill kinetics compared with the first-line MRSA antibiotic, vancomycin, and also conferred significant protection from mortality in a murine model of systemic lethal MRSA infection. These data emphasize the utility of the marine environment as a relatively untapped source of antibiotics against major drug-resistant human pathogens. These studies will also guide future isolation and preclinical development of depsipeptide anti-MRSA compounds from marine-derived actinomycetes.
耐甲氧西林金黄色葡萄球菌（HA-和 CA-MRSA）医院和社区相关性感染的惊人上升促使人们迫切地寻找新型抗生素。我们从斐济海岸分离出的放线菌物种中发现了链阳菌素艾米丁，这是首次从海洋微生物中鉴定出这种抗生素。从该菌株（CNS-575）中提取并纯化了艾米丁，并通过 2D NMR 光谱鉴定为三旋转体种类。艾米丁在微量肉汤稀释测定中对 HA-和 CA-MRSA 表现出很强的活性，对 HA-和 CA-MRSA 菌株的最低抑菌浓度（MIC）低至 1-2 mg l(-1)。此外，艾米丁对其他革兰氏阳性菌和几种革兰氏阴性病原体也具有活性，在高于 MIC 20 倍以上的浓度下也没有细胞毒性。艾米丁与一线抗 MRSA 抗生素万古霉素相比表现出良好的时效杀灭动力学，并且在 MRSA 全身致死性感染的小鼠模型中也能显著提高存活率。这些数据强调了海洋环境作为针对主要耐药性人类病原体的抗生素相对未开发来源的实用性。这些研究还将指导未来从海洋衍生放线菌中分离和临床前开发抗 MRSA 化合物。
