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.
Keywords: Escherichia coli; OxyR; bacterial gene networks; bacterial populations; cell interactions; oxidative stress; phenotypic heterogeneity; single-cell imaging; stress response; transcription regulation.
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