抗生素耐药性的生理成本:从细菌中的核糖体变体的洞察力
Eun Chae Moon1, Tushar Modi2, Dong-Yeon D Lee3
1Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA.
Science advances
|November 15, 2024
概括
细菌的抗生素耐药性付出了代价. 在Bacillus subtilis中,一种特定的核糖体变体 (L22*) 显示在 (Mg2+) 限制下,由于细胞内Mg2+和ATP水平较低,生长减少.
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:
- 抗生素耐药性是一个日益增长的全球健康威胁.
- 细菌核糖体变种可以赋予抗生素耐药性.
- 抗生素耐药性核糖体变异的生理影响尚不清楚.
研究的目的:
- 为了研究自然存在的抗生素耐药核糖体变体 (L22*) 在 Bacillus subtilis.的生理后果.
- 为了确定 (Mg2+) 在L22*变种的健康状况中的作用.
- 阐明任何观察到的健身成本背后的机制.
主要方法:
- 在不同的Mg2+条件下对比L22*和野生型 (WT) Bacillus subtilis的培竞争实验.
- 测量细胞内Mg2+水平.
- 核糖体形状动态的粗粒度弹性网络建模.
- 测量细胞中的腺5'-三酸盐 (ATP) 水平.
主要成果:
- 与WT相比,Mg2+限制显著阻碍了L22*变种的生长,即使有抗生素压力.
- 这种L22*变异显示了细胞内Mg2+水平的降低,而不是更低的核糖体丰度.
- 结构建模表明L22*核糖体与Mg2+的结合更加紧密.
- 实验证实了在Mg2+限制下,L22*细胞中的ATP水平预测下降.
结论:
- 抗生素耐药的核糖体变体可能会产生与Mg2+平衡相关的生理成本.
- 对于细胞内Mg2+的竞争可以抑制抗生素耐药变体的建立.
- 了解这些权衡对于打击抗生素耐药性至关重要.
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