代谢中断会损害核糖体蛋白水平,导致氨基糖化物耐受性提高
Rauf Shiraliyev1, Mehmet A Orman1
1William A. Brookshire Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States.
eLife
|August 2, 2024
概括
变异性大肠杆菌与改变的能量代谢表现出增强的aminoglycoside抗生素耐受性. 这种耐受性与增加的三酸循环活性和减少与核糖体相关的过程有关,为抗性细菌提供了新的策略.
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 生化学
背景情况:
- 氨基甘油酸抗生素对于通过向细菌核糖体来治疗细菌感染至关重要.
- 了解抗生素耐受性的机制对于开发针对耐药细菌的有效治疗至关重要.
研究的目的:
- 为了研究在能量代谢有缺陷的大肠杆菌菌株中氨基糖化物耐受性增加背后的机制.
- 探索能代谢,质子动力和耐受性细菌菌株中氨基糖化物吸收之间的关系.
主要方法:
- 产生了与能量代谢有关的大肠杆菌的淘汰菌株.
- 测量了质子运动力和细胞内氨基糖化物水平.
- 进行了全面的蛋白质组学分析和途径丰富分析.
主要成果:
- 突变菌株在指数增长的中期表现出增加的氨基糖化物耐受性.
- 在突变菌株中没有观察到质子驱动力或氨基糖化物吸收的显著减少.
- 蛋白质组学揭示了三碳酸 (TCA) 循环蛋白的上调和核糖体蛋白和突变菌株的生物发生路径的下调.
结论:
- 增加的TCA循环活性可以弥补能量代谢干扰,保持膜潜力和耐受性菌株的ATP水平.
- 核糖体通路的下调提供了对氨基糖化物耐受性的合理解释.
- 研究结果提供了关于氨基糖化物耐受性机制和克服细菌耐药性的潜在策略的见解.
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