Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria
Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria
复制标题
DOI：
10.1073/pnas.0711712105
复制
发表时间：
2008-04-22
影响因子：
11.1
通讯作者：
Balaban, Nathalie Q.
中科院分区：
文献类型：
--
作者：
Gefen, Orit;Gabay, Chana;Balaban, Nathalie Q.
细胞群体中的表型变异性与对应激条件的进化稳健性有关。细胞间变异性的重要性的一个显著例子是细菌持久性，其中休眠细菌的亚群，称为持久性，被证明是负责人口的持久性抗生素治疗。在这里，我们使用微流控装置来监测合成启动子下荧光蛋白的诱导，并表征单个持久细菌的休眠状态。令人惊讶的是，我们观察到蛋白质的产生确实发生在假定的休眠细菌中，在从稳定期退出后的一个狭窄的时间窗口内。只有在此之后，蛋白质的生产才会停止，这表明在这个时间窗口内，而不是像以前认为的那样，在饥饿期间，分化成持久性完全发展。实际上，我们观察到在此时间窗内细菌暴露于抗生素显著降低了持久性。我们的研究结果指出了对抗持续性细菌感染的新策略。在这项研究中提出的单细胞诱导的定量测量应该揭示导致不同系统中亚群休眠的过程，例如在存活但不可培养的细菌亚群或静止癌细胞亚群中。
Phenotypic variability in populations of cells has been linked to evolutionary robustness to stressful conditions. A remarkable example of the importance of cell-to-cell variability is found in bacterial persistence, where subpopulations of dormant bacteria, termed persisters, were shown to be responsible for the persistence of the population to antibiotic treatments. Here, we use microfluidic devices to monitor the induction of fluorescent proteins under synthetic promoters and characterize the dormant state of single persister bacteria. Surprisingly, we observe that protein production does take place in supposedly dormant bacteria, over a narrow time window after the exit from stationary phase. Only thereafter does protein production stop, suggesting that differentiation into persisters fully develops over this time window and not during starvation, as previously believed. In effect, we observe that exposure of bacteria to antibiotics during this time window significantly reduces persistence. Our results point to new strategies to fight persistent bacterial infections. The quantitative measurement of single-cell induction presented in this study should shed light on the processes leading to the dormancy of subpopulations in different systems, such as in subpopulations of viable but nonculturable bacteria, or those of quiescent cancer cells.