A universal tradeoff between growth and lag in fluctuating environments

The rate of cell growth is crucial for bacterial fitness and a main driver of proteome allocation(1,2), but it is unclear what ultimately determines growth rates in different environmental conditions. Increasing evidence suggests that other objectives also play key roles(3–7), such as the rate of physiological adaptation to changing environments(8,9). The challenge for cells is that these objectives often cannot be independently optimized, and maximizing one often reduces another. Many such tradeoffs have indeed been hypothesized, based on qualitative correlative studies(8–11). Here we report the occurrence of a tradeoff between steady-state growth rate and physiological adaptability for Escherichia coli, upon abruptly shifting a growing culture from a preferred carbon source to fermentation products such as acetate. Such transitions, common for enteric bacteria, are often accompanied by multi-hour lags before growth resumes. Metabolomic analysis revealed that the long lags resulted from the depletion of key metabolites due to the sudden reversal of central carbon flux imposed by these nutrient shifts. A model of sequential flux limitation not only explained the observed universal tradeoff between growth and adaptability, but also generated quantitative predictions that were validated experimentally. The observed trade-off reflects the opposing enzyme requirements for glycolysis versus gluconeogenesis.