Environmental Dependence of Stationary-Phase Metabolism in Bacillus subtilis and Escherichia coli

When microbes lack the nutrients necessary for growth, they enter stationary phase. In cases when energy sources are still present in the environment, they must decide whether to continue to use their metabolic program to harvest the available energy. Here we characterized the metabolic response to a variety of types of nutrient starvation in Escherichia coli and Bacillus subtilis. We found that E. coli exhibits a range of phenotypes, with the lowest metabolic rates under nitrogen starvation and highest rates under magnesium starvation. In contrast, the phenotype of B. subtilis was dominated by its decision to form metabolically inactive endospores. While its metabolic rates under most conditions were thus lower than those of E. coli, when sporulation was suppressed by a genetic perturbation or an unnatural starvation condition, the situation was reversed. To further probe stationary-phase metabolism, we used quantitative metabolomics to investigate possible small-molecule signals that may regulate the metabolic rate of E. coli and initiate sporulation in B. subtilis. We hypothesize a role for phosphoenolpyruvate (PEP) in regulating E. coli glucose uptake and for the redox cofactors NAD(H) and NADP(H) in initiation of sporulation. Our work is directly relevant to synthetic biology and metabolic engineering, where active metabolism during stationary phase, which uncouples production from growth, remains an elusive goal.