Graduate School of Fundamental Science and Technology, Center for Biosciences and Informatics, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
Department of Biosciences and Informatics, Keio University, Yokohama, Kanagawa, 223-8522, Japan.
Sci Rep. 2022 Oct 26;12(1):17946. doi: 10.1038/s41598-022-22189-x.
In fluctuating environments, many microorganisms acquire phenotypic heterogeneity as a survival tactic to increase the likelihood of survival of the overall population. One example of this interindividual heterogeneity is the diversity of ATP concentration among members of Escherichia coli populations under glucose deprivation. Despite the importance of such environmentally driven phenotypic heterogeneity, how the differences in intracellular ATP concentration emerge among individual E. coli organisms is unknown. In this study, we focused on the mechanism through which individual E. coli achieve high intracellular ATP concentrations. First, we measured the ATP retained by E. coli over time when cultured at low (0.1 mM) and control (22.2 mM) concentrations of glucose and obtained the chronological change in ATP concentrations. Then, by comparing these chronological change of ATP concentrations and analyzing whether stochastic state transitions, periodic oscillations, cellular age, and intercellular communication-which have been reported as molecular biological mechanisms for generating interindividual heterogeneity-are involved, we showed that the appearance of high ATP-holding individuals observed among E. coli can be explained only by intercellular transmission. By performing metabolomic analysis of post-culture medium, we revealed a significant increase in the ATP, especially at low glucose, and that the number of E. coli that retain significantly higher ATP can be controlled by adding large amounts of ATP to the medium, even in populations cultured under control glucose concentrations. These results reveal for the first time that ATP-mediated intercellular transmission enables some individuals in E. coli populations grown at low glucose to retain large amounts of ATP.
在波动的环境中，许多微生物会获得表型异质性，作为一种生存策略，以增加整体种群存活的可能性。这种个体间异质性的一个例子是，在葡萄糖缺乏的情况下，大肠杆菌种群中 ATP 浓度的多样性。尽管这种由环境驱动的表型异质性非常重要，但个体大肠杆菌体内的细胞内 ATP 浓度差异是如何产生的还不得而知。在本研究中，我们专注于个体大肠杆菌如何实现高细胞内 ATP 浓度的机制。首先，我们测量了在低（0.1 mM）和对照（22.2 mM）葡萄糖浓度下培养大肠杆菌时，其细胞内 ATP 随时间的保留情况，并获得了 ATP 浓度的时程变化。然后，通过比较这些 ATP 浓度的时程变化，并分析随机状态转换、周期性振荡、细胞年龄和细胞间通讯等是否参与其中，这些都被报道为产生个体间异质性的分子生物学机制，我们表明，在大肠杆菌中观察到的高 ATP 保留个体的出现只能通过细胞间传递来解释。通过对培养后培养基进行代谢组学分析，我们发现 ATP 含量显著增加，特别是在低葡萄糖条件下，并且通过向培养基中添加大量 ATP，可以控制保留显著更高 ATP 的大肠杆菌数量，即使在对照葡萄糖浓度下培养的种群中也是如此。这些结果首次揭示了 ATP 介导的细胞间传递使低葡萄糖培养的大肠杆菌种群中的一些个体能够保留大量的 ATP。
