不同的碳来源利用驱动了抗生素耐受性持久细胞的代谢状态和复苏
Yufei Sun1, Sweta Roy2, Qingbo Yang3
1Department of Energy, Environmental, and Chemical Engineering, Washinton University in St. Louis, St. Louis, MO, United States.
Frontiers in pharmacology
|September 19, 2025
概括
持久性细胞对于持久性感染至关重要,表现出显著降低的新陈代谢,特别是在酸盐条件下. 了解这些代谢变化为细菌抗生素耐受性提供了新的策略.
科学领域:
- 微生物学 微生物学
- 代谢工程是代谢工程.
- 细菌生理学 细菌生理学
背景情况:
- 持续性细菌感染是一个重大的临床挑战,因为耐受抗生素的休眠性持续性细胞.
- 持久性细胞是具有高抗生素耐受性的表型变异,能够在抗生素被移除后恢复生长.
- 细菌持久性和复苏的代谢适应性尚未完全理解.
研究的目的:
- 为了研究大肠杆菌的代谢活动,细胞在不同的碳来源下持续存在.
- 为了阐明细菌持久性期间发生的代谢转变.
- 为了确定对抗抗生素耐受性细菌的潜在目标.
主要方法:
- 诱导大肠杆菌的持久细胞使用碳酸m-甲化 (CCCP).
- 稳定的同位素标记为C-葡萄糖和C-酸盐.
- 通过LC-MS和GC-MS对代谢中间体和氨基酸的标签纳入量化.
主要成果:
- 与正常细胞相比,持久性细胞的代谢活性显著降低.
- 延迟的标记动态在持续的中心代谢途径 (酸途径,TCA循环) 中观察到.
- 在酸盐条件下,持久性表现出更深层次的代谢关闭,表明碳源依赖的适应.
结论:
- 细菌持续性细胞代谢是适应性的,并显著减少,随着可用的碳来源而变化.
- 这些发现为抗生素耐受性持久细胞的代谢策略提供了关键的见解.
- 了解持久性新陈代谢可以指导开发针对持久性细菌感染的新疗法.
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