Suboptimal resource allocation in changing environments constrains response and growth in bacteria. Issue 12 (20th December 2021)

• Record Type: Journal Article
• Authors: Balakrishnan, Rohan; de Silva, Roshali T; Hwa, Terence; Cremer, Jonas
• Is Part Of: Molecular systems biology. Volume 17:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-20
• Subjects: cellular response -- diauxie -- environmental changes -- growth optimality -- resource allocation; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.202110597
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract: To respond to fluctuating conditions, microbes typically need to synthesize novel proteins. As this synthesis relies on sufficient biosynthetic precursors, microbes must devise effective response strategies to manage depleting precursors. To better understand these strategies, we investigate the active response of Escherichia coli to changes in nutrient conditions, connecting transient gene expression to growth phenotypes. By synthetically modifying gene expression during changing conditions, we show how the competition by genes for the limited protein synthesis capacity constrains cellular response. Despite this constraint cells substantially express genes that are not required, trapping them in states where precursor levels are low and the genes needed to replenish the precursors are outcompeted. Contrary to common modeling assumptions, our findings highlight that cells do not optimize growth under changing environments but rather exhibit hardwired response strategies that may have evolved to promote fitness in their native environment. The constraint and the suboptimality of the cellular response uncovered provide a conceptual framework relevant for many research applications, from the prediction of evolution to the improvement of gene circuits in biotechnology. SYNOPSIS: Analyses of how allocation of cellular resources to different genes shapes Escherichia coli 's response to changing nutrient conditions show that growth transitions are determined by the competition between genes that are directly required in the encountered conditions and those that are not. Synthetic titration constructs are used to characterize how growth recovery during diauxic shifts varies with allocation of gene expression resources towards different genes. A low‐dimensional model predicts how the allocation of resources affects the dynamics of growth transitions. Bacterial response includes the substantial expression of non‐required genes explaining the diauxic transitions to many different carbon sources. Abstract : Analyses of how allocation of cellular resources to different genes shapes Escherichia coli 's response to changing nutrient conditions show that growth transitions are determined by the competition between genes that are directly required in the encountered conditions and those that are not.