RT Journal Article
SR Electronic
T1 The energy requirements of ion homeostasis determine the lifespan of starving bacteria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.22.469587
DO 10.1101/2021.11.22.469587
A1 Severin Schink
A1 Mark Polk
A1 Edward Athaide
A1 Avik Mukherjee
A1 Constantin Ammar
A1 Xili Liu
A1 Seungeun Oh
A1 Yu-Fang Chang
A1 Markus Basan
YR 2021
UL http://biorxiv.org/content/early/2021/11/22/2021.11.22.469587.abstract
AB The majority of microbes on earth, whether they live in the ocean, the soil or in animals, are not growing, but instead struggling to survive starvation1–6. Some genes and environmental conditions affecting starvation survival have been identified7–13, but despite almost a century of study14–16, we do not know which processes lead to irreversible loss of viability, which maintenance processes counteract them and how lifespan is determined from the balance of these opposing processes. Here, we used time-lapse microscopy to capture and characterize the cell death process of E. coli during carbon starvation for the first time. We found that a lack of nutrients results in the collapse of ion homeostasis, triggering a positive-feedback cascade of osmotic swelling and membrane permeabilization that ultimately results in lysis. Based on these findings, we hypothesized that ion transport is the major energetic requirement for starving cells and the primary determinant of the timing of lysis. We therefore developed a mathematical model that integrates ion homeostasis and ‘cannibalistic’ nutrient recycling from perished cells16,17 to predict lifespan changes under diverse conditions, such as changes of cell size, medium composition, and prior growth conditions. Guided by model predictions, we found that cell death during starvation could be dramatically slowed by replacing inorganic ions from the medium with a non-permeating osmoprotectant, removing the cost of ion homeostasis and preventing lysis. Our quantitative and predictive model explains how survival kinetics are determined in starvation and elucidates the mechanistic underpinnings of starvation survival.Competing Interest StatementThe authors have declared no competing interest.