Department of Biochemistry, University of Oxford, Oxford, UK.
Department of Biochemistry, University of Oxford, Oxford, UK; Department of Biology, University of Oxford, Oxford, UK; Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
Cell Syst. 2024 Nov 20;15(11):1033-1045.e6. doi: 10.1016/j.cels.2024.10.003.
Bacteria employ diverse gene regulatory networks to survive stress, but deciphering the underlying logic of these complex networks has proved challenging. Here, we use time-resolved single-cell imaging to explore the functioning of the E. coli regulatory response to oxidative stress. We observe diverse gene expression dynamics within the network. However, by controlling for stress-induced growth-rate changes, we show that these patterns involve just three classes of regulation: downregulated genes, upregulated pulsatile genes, and gradually upregulated genes. The two upregulated classes are distinguished by differences in the binding of the transcription factor, OxyR, and appear to play distinct roles during stress protection. Pulsatile genes activate transiently in a few cells for initial protection of a group of cells, whereas gradually upregulated genes induce evenly, generating a lasting protection involving many cells. Our study shows how bacterial populations use simple regulatory principles to coordinate stress responses in space and time. A record of this paper's transparent peer review process is included in the supplemental information.
细菌利用多种基因调控网络来应对压力,但要破解这些复杂网络的底层逻辑一直具有挑战性。在这里,我们使用时间分辨的单细胞成像技术来探索大肠杆菌对氧化应激的调控反应的功能。我们观察到网络内存在多样化的基因表达动力学。然而,通过控制应激诱导的生长速率变化,我们表明这些模式只涉及三类调控:下调基因、上调脉冲基因和逐渐上调基因。上调的两类基因因转录因子 OxyR 的结合差异而区分开来,并且在应激保护过程中似乎发挥不同的作用。脉冲基因在少数细胞中短暂激活,以对一组细胞进行初始保护,而逐渐上调的基因均匀诱导,产生涉及许多细胞的持久保护。我们的研究表明,细菌群体如何利用简单的调控原则来协调时空上的应激反应。该论文的透明同行评审过程记录包含在补充信息中。