Activity of the streptogramin antibiotic etamycin against methicillin-resistant Staphylococcus aureus.
Activity of the streptogramin antibiotic etamycin against methicillin-resistant Staphylococcus aureus.
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DOI：
10.1038/ja.2010.22
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发表时间：
2010-05
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--
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医院和社区相关的耐甲氧西林金黄色葡萄球菌（HA-和CA-MRSA）感染的惊人增加促使人们迫切寻找新型抗生素。我们首次从新发现的海洋放线菌中发现了链霉素抗生素依霉素，并表征了其对抗一组 HA-和 CA-MRSA 菌株的活性。依他霉素是从以前未表征的海洋来源放线菌（指定为 CNS-575 菌株）中提取和纯化的，通过二维核磁共振 (NMR) 光谱测定为三旋转异构体。在微肉汤稀释试验中，Etamycin 对医院和社区相关的 MRSA 菌株表现出有效的活性，对 HA 和 CA-MRSA 菌株的最低抑制浓度 (MIC) 低至 1 – 2 mg/L。此外，依霉素还对其他革兰氏阳性和几种革兰氏阴性病原体具有活性，并且被发现在浓度高于 MIC 20 倍以上时没有细胞毒性。与一线 MRSA 抗生素万古霉素相比，Etamycin 表现出良好的时间杀灭动力学，并且在全身致死性 MRSA 感染的小鼠模型中具有显着的死亡率保护作用。这些数据强调了海洋环境作为相对未开发的针对主要耐药人类病原体的抗生素来源的效用。这些研究还将指导未来从海洋放线菌中分离和临床前开发缩酚肽抗 MRSA 化合物。
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 antibiotic, etamycin, for the first time from a newly discovered marine actinomycete and characterized its activity against a panel of HA- and CA-MRSA strains. Etamycin was extracted and purified from a previously uncharacterized marine-derived actinomycete, designated strain CNS-575, as a three-rotamer species as determined by two-dimensional nuclear magnetic resonance (NMR) spectroscopy. Etamycin demonstrated potent activity against hospital- and community-associated strains of MRSA in microbroth dilution assays, with minimum inhibitory concentrations (MIC) as low as 1 – 2 mg/L 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 the MIC. Etamycin displayed favorable time-kill kinetics compared to 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.
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