Extracellular metabolite dynamics and temporal organization of metabolic function in E. coli

Bacteria dynamically exchange with their environment by constantly uptaking nutrients and secreting metabolic products and other biomolecules. While such secreted metabolites may represent a high-level reporter of metabolic activity of the culture, relatively few studies have focused on their characterization. In addition, metabolites may be potential mediators of intercellular interactions. This study aims at identifying candidate mediators of intercellular exchanges and population behavior from temporal patterns of metabolites. To do this, we used capillary electrophoresis mass spectrometry (CE-MS) to monitor secreted metabolites in synchronized continuous culture of E. coli displaying respiratory oscillations. We observed that multiple metabolites are secreted in significant quantities in the extracellular medium, including amino acids and other intermediates of central metabolism. Some of the secreted metabolite dynamics appear linked to the known valine toxicity in E. coli and are also associated with the respiratory oscillations and their dynamics. Moreover, the dynamics in the level of several amino acids appeared well correlated, suggesting organized cycles of secretion/reuptake during respiratory and metabolic shifts linked to valine levels. Overall, the current results suggest that multiple metabolites are produced and likely exchanged by E. coli during continuous growth. These appear to reflect the internal metabolic state of the cell and may form an underappreciated level of information exchange that cell populations use to coordinate activities.