通过Cfr介导的抗菌素耐药性的结构基础以及规避它的机制
Elena V Aleksandrova1, Kelvin J Y Wu2, Ben I C Tresco2
1Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Nature chemical biology
|January 18, 2024
概括
通过修改细菌核糖体,Cfr甲基酶会导致抗生素耐药性. 结构研究揭示了这种修饰,在23S核糖体RNA中A2503的C8甲基化,如何改变核糖体结构和抗生素结合.
科学领域:
- 细菌核糖体的结构和功能.
- 抗生素耐药性的机制
- 分子生物学和结构生物化学.
背景情况:
- 细菌核糖体是抗生素的关键目标.
- 基转移酶中心 (PTC) 是许多抗生素的目标.
- 在23S核糖体RNA中Cfr甲基酶介导的A2503的C8甲基化是一种普遍的抗性机制.
研究的目的:
- 阐明Cfr介导的抗生素耐药性的分子机制.
- 为了确定Cfr修饰核糖体的高分辨率结构.
- 了解Cfr修饰如何影响抗生素的结合和效力.
主要方法:
- 高分辨率结构分析 (例如,冷电磁或X射线结晶学).
- 生物化学测试以评估抗生素的结合和抑制.
- 原生和Cfr-修改的核糖体的结构比较.
主要成果:
- 确定了Cfr-修饰的70S核糖体与结合tRNA的高分辨率结构.
- 通过Cfr介导的A2503甲基化会诱导核酸A2062.2.的性重组.
- 获得了对抗生素iboxamycin和tylosin与修改后的核糖体结合的结构见解.
结论:
- 这项研究为Cfr介导的抗生素耐药性提供了原子水平的理解.
- 核糖体中的全变化有助于降低抗生素的疗效.
- 结构数据显示不同抗生素在耐药核糖体上具有不同的结合模式.
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