膜蛋白的错误翻译和双组件系统的激活触发了抗生素介导的细胞死亡
Michael A Kohanski1, Daniel J Dwyer, Jamey Wierzbowski
1Department of Biomedical Engineering, Center for BioDynamics, and Center for Advanced Biotechnology, Boston University, Boston, MA 02215, USA.
Cell
|November 18, 2008
概括
氨基甘油酸抗生素通过氧化应激导致细菌细胞死亡,与错误折叠的膜蛋白有关. 包膜和氧化还原反应系统是这种杀菌机制的关键.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 氨基甘油酸抗生素 (例如,甘胺,甘胺) 向细菌的核糖体.
- 氨基糖化物诱导的细菌细胞死亡的精确机制,特别是杀菌作用,仍然不完全理解.
- 氧化应激越来越被认为是导致杀菌性抗生素作用的因素.
研究的目的:
- 阐明氨基糖化物诱导氧化应激和细胞死亡的途径.
- 为了确定关键的分子参与者和参与氨基糖化物中介杀伤的信号通路.
- 为了确定这些途径是否与其他杀菌抗生素共同存在.
主要方法:
- 采用了系统级的方法.
- 进行了表型分析.
- 使用了针对膜蛋白交通系统的基因操纵.
主要成果:
- 氨基糖化物诱导的氧化应激和细胞死亡严重依赖于膜蛋白的错误翻译和错误折叠.
- 在这个过程中,通过外应力响应双组件系统发送信号至关重要.
- 氧化还原反应的两组系统也起着重要作用.
- 这些两组系统广泛参与各种杀菌抗生素诱导的氧化应激和细胞死亡.
结论:
- 错误折叠的膜蛋白和随后的氧化应激是aminoglycoside杀菌作用的核心.
- 包膜和氧化还原反应的两组系统是氨基糖化物诱导的细胞死亡的关键媒介.
- 这些发现揭示了杀菌抗生素所使用的共同杀死机制,增强了我们对抗生素作用的理解.
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