Bacterial gene expression dynamics in the regime of vanishing growth

In order to grow and survive in different environment, bacteria display a remarkable phenotypic plasticity. This is accomplished by relatively precise gene regulation. Notwithstanding, gene expression is a noisy phenomenon, and the infinite combination of conditions bacteria can face make it impossible for a response based only on sensors to take place. In addition, most of those regulatory systems have been studied in steady state, fast exponential growth conditions, even though most bacteria spend a substantial part of their lifetime in a non growing state, owing to the lack of nutrient in their habitat.
In this work, we investigate the effect of slow or no growth on the gene regulation dynamics.
We demonstrate how the growth-induced dilution of regulatory-switches inducers results in increased sensitivity of the regulatory circuits at low growth rate. In addition to allowing bacteria to easier adapt their phenotype when condition are unfavourable, we demonstrate, using microfluidics coupled with time lapse fluorescence microscopy, that this growth-coupled sensitivity implements an optimal mechanism of sugar preference where bacteria start growing on a new sugar only if the growth thus achieved is higher than the current one.
We subsequently review the literature on quantitative biology of E. coli starvation, in order to highlights firmly established features and knowledge gaps in the phenomenology, phenotypic characteristics and regulatory systems of bacterial starvation, as well as survival and regrowth capacity of starved bacteria. Throughout this review we underline the existing quantitative relations that have been established between those different aspects, e.g. dormancy depth and stress tolerance, and advocate for the need to identify the relevant parameters to further explore those relations. We believe that those phenomenological relations will help to progress in our understanding of the evolutionary strategies that underlay starvation response(s).
Finally, we study the expression dynamics of about 20 promoters in individual bacteria as we switch them from exponential growth to starvation. We find that promoters display a variety of responses, going from instantaneous arrest at the entry into starvation to progressive decay, sometimes even peaking at the point of growth arrest. We demonstrate that the delay between the arrest of growth and that of gene expression results in a substantial and promoter-dependent accumulation of protein. We show that this response is remarkably homogeneous across single cells of the population, and that it sets the phenotype of bacteria for days. In accordance with this result, we demonstrate that the early gene expression at the onset of starvation is critical to survive an oxidative stress challenge coming 20h later. This suggest that the regulatory response at the onset of starvation is not adaptive, but rather preventive.
This work highlights the necessity of considering non-growing states and passives mechanisms to understand bacterial physiology, metabolism and evolutionary history, and opens the door on new regulatory strategies implemented by bacteria to cope with the challenges presented by their environment.