一种双重机制的抗生素杀死了格拉姆阴性细菌,避免了抗药性
James K Martin1, Joseph P Sheehan1, Benjamin P Bratton2
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell
|June 5, 2020
概括
一种新型化合物SCH-79797同时针对两种细菌通路,为抗生素耐药性低耐药性格拉姆阴性和格拉姆阳性细菌提供了有效的策略. 它的衍生物Irresistin-16在临床前模型中显示有效性.
科学领域:
- 微生物学
- 药物发现
- 抗菌药物耐药性
背景情况:
- 抗生素耐药性构成了全球卫生危机,
- 现有的治疗方法对耐药菌株如甲素耐药黄金葡萄球菌 (MRSA) 的效果越来越差.
研究的目的:
- 描述一种新型化合物,SCH-79797,具有针对耐药细菌的双重向作用机制 (MoA).
- 开发和评估一种更强效的衍生药物Irresistin-16,用于治疗具有挑战性的细菌感染.
主要方法:
- 使用定量成像,蛋白质学,遗传学,代谢学和基于细胞的测试来阐明SCH-79797的MOA.
- 对SCH-79797及其衍生物Irresistin-16进行了检测,对包括MRSA和Neisseria gonorrhoeae在内的格兰阴性和格兰阳性细菌进行了检测.
- 使用小鼠阴道感染模型来评估Irresistin-16的体内疗效.
主要成果:
- SCH-79797具有独特的双重MoA,针对叶酸代谢和细菌膜完整性.
- 这种化合物表现出难以检测的低耐药性频率,并且优于对MRSA持久菌的组合疗法.
- 在临床前的小鼠模型中,Irresistin-16 显示出对尼塞利亚淋病的强效和有效性.
结论:
- 将多个MOA结合到一个单一的分子是开发新抗生素来对抗难以治疗的病原体的有希望的策略.
- SCH-79797和Irresistin-16为新型抗菌疗法提供了有希望的线索,以应对抗生素耐药性日益严重的威胁.
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