Biology subjects

Schink, S. J.

Publications and source records attributed to Schink, S. J..

4 recordsLinked to original sources

bioRxiv2022

Adaptation of bacterial proteome reveals a key role of the cell envelope in starvation survival

Bacteria reorganize their physiology upon entry to stationary phase. What part of this reorganization improves starvation survival is a difficult question, because the change in physiology includes a global reorganization of the proteome, envelope and metabolism of the cell. In this work, we used several trade-offs between fast growth and long survival to statistically score over 2000 E. coli proteins for their global correlation with death rate. The combined ranking allowed us to narrow down the set of proteins that positively correlate with survival and validate the causal role of a subset of proteins. Remarkably, we found that important survival genes are related to the cell envelope, i.e., periplasm and outer membrane, because maintenance of envelope integrity of E. coli plays a crucial role during starvation. Our results uncover a new protective feature of the outer membrane that adds to the growing evidence that the outer membrane is not only a barrier that prevents abiotic substances from reaching the cytoplasm, but essential for bacterial proliferation and survival. Standfirst textA trade-off between the two major modes of bacterial lifestyle, growth and starvation can be explained by bacteria investing resources into the cell envelope to make it impermeable to ions, which improves their lifespan but comes at the expense of slowing down growth. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/492425v2_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@7534d7org.highwire.dtl.DTLVardef@e02e43org.highwire.dtl.DTLVardef@1fd4acdorg.highwire.dtl.DTLVardef@39e716_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA trade-off between growth rate and death rate confines fitness of bacteria across environments. C_LIO_LIAnalysis of proteome signatures in 126 conditions across five independent perturbations reveals the cell envelope as a key determinant of death rate. C_LIO_LIThe trade-off can be abolished by changing environment to a low-salt, but osmo-balanced medium where cell envelope integrity is not limiting. C_LI

systems biology↗

bioRxiv2021

The energy requirements of ion homeostasis determine the lifespan of starving bacteria

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.

microbiology↗

bioRxiv2021

A thermal fuse in methionine biosynthesis arrests growth and protects Escherichia coli at elevated temperatures

Adaptive stress resistance in microbes is mostly attributed to the expression of stress response genes, such as heat shock proteins, which prevent deterioration of cellular material. Here, we report a novel response of E. coli to heat stress: induction of a growth-arrested state, caused by degradation of an enzyme in the methionine biosynthesis pathway (MetA). While MetA degradation is detrimental for proliferation, we show that the resulting growth arrest has a direct benefit for survival at high temperatures; it protects cells when temperatures rise beyond 50{degrees}C, increasing the survival chances by over 1000-fold. Using a combination of experiments and mathematical modelling, we show that degradation of MetA leads to the coexistence of growing and non-growing cells, allowing microbes to bet-hedge between continued growth if conditions remain bearable and survival if conditions worsen. We test our model experimentally and verify quantitatively how protein expression, degradation rates and environmental stresses affect the partitioning between growing and non-growing cells. Because growth arrest can be abolished with simple mutations, such as point mutations of MetA and knock-outs of proteases, we interpret the breakdown of methionine synthesis as a system that has evolved to disintegrate at high temperature and shut off growth, analogous to thermal fuses used in engineering to shut off electricity when the device could be damaged by overheating.

microbiology↗

bioRxiv2021

Trade-offs in adaptation to glycolysis and gluconeogenesis result in a preferential flux direction in central metabolism

Central carbon metabolism is highly conserved across microbial species, but can catalyze very different pathways depending on the organism and their ecological niche. Here, we study the dynamic re-organization of central metabolism after switches between the two major opposing pathway configurations of central carbon metabolism, glycolysis and gluconeogenesis in Escherichia coli, Pseudomonas aeruginosa and Pseudomonas putida. We combined growth dynamics and dynamic changes of intracellular metabolite levels with a coarse-grained model that integrates fluxes, regulation, protein synthesis and growth and uncovered fundamental limitations of the regulatory network: after nutrient shifts, metabolite concentrations collapse to their equilibrium, rendering the cell unable to sense which direction the flux is supposed to flow through the metabolic network. The cell can partially alleviate this by picking a preferred direction of regulation at the expense of increasing lag times in the opposite direction. Moreover, decreasing both lag times simultaneously comes at the cost of reduced growth rate or higher futile cycling between metabolic enzymes. These three trade-offs can explain why microorganisms specialize for either glycolytic or gluconeogenic substrates and can help elucidate the complex growth patterns exhibited by different microbial species. Graphical synopsis O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY Standfirst textMicrobes face a series of fundamental trade-offs that limit their ability to optimize simultaneously for both glycolytic and gluconeogenic growth. Bullet pointsO_LILag times between glycolysis and gluconeogenesis show asymmetry in many microbes: A long lag in one direction, but a short lag in the other. C_LIO_LILong lag times are caused by an inability to sense fluxes after nutrient shifts. C_LIO_LIWith existing regulation, lag time asymmetry can only be overcome by reducing either growth rate or increasing futile cycling in metabolism. C_LI

systems biology↗