The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time
Year: 2024
Type: article
Abstract: Bacteria employ diverse gene regulatory networks to protect themselves from stressful environments. While transcriptomics and proteomics show that the expression of different genes can shift strongly in response to stress, the underlying logic of large regulatory networks is difficult to understand from bulk measurements performed at discrete time points. As a result, it remains challenging to predict how these regulatory networks function at a system level. Here we use time-resolved single-cell imaging to explore the functioning of a key bacterial stress response: The Escherichia coli response to oxidative stress. Our work reveals a striking diversity in the expression dynamics of genes in the regulatory network, with differences in the timing, magnitude, and direction of expression changes. Nevertheless, we find that these patterns have a simple underlying logic. Firstly, all genes exhibit a transient increase in their protein levels simply due to the slowing down of cell growth under stress. Controlling for this effect reveals three classes of gene regulation driven by the transcription factor OxyR. Downregulated genes drop in expression level, while upregulated genes either show pulsatile expression that decays rapidly or gradual induction, dependent upon transcription factor binding dynamics. These classes appear to serve distinct functional roles in cell populations. Pulsatile genes are stress-sensitive and activate rapidly and transiently in a few cells, which provides an initial protection for cell groups. Gradually upregulated genes are less sensitive and induce more evenly generating a lasting protection that involves a larger number of cells. Our study shows how bacterial populations use simple regulatory principles to coordinate a stress response in space and time.
Source: Cell Systems
Institution: University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Awards: G339059223, Stochastic variation and regulation of bacterial DNA repair and mutagenesis, Understanding and engineering complex microbial communities, The Evolution of Bacterial Warfare, Understanding and engineering complex microbial communities, Stochastic variation and regulation of bacterial DNA repair and mutagenesis, G9000004879
OpenAlex ID: W4404434210