Acetate promotes nutritional adaptation in Escherichia coli

The long-held view that acetate, one of the main fermentation by-products of Escherichia coli , is toxic to microbial growth is currently challenged. Here, we demonstrate that acetate promotes E. coli adaptation to nutrient changes by accelerating growth resumption, with as little as 250 µM acetate being sufficient to shorten the lag phase by several hours. Acetate was found to be consumed via acetyl-CoA synthetase very early after the nutrient change. Transcriptomics, metabolomics and ¹³ C-isotope labeling experiments show that acetate replenishes metabolic pools in the tricarboxylic acid cycle and upper glycolysis. Single-cell analyses reveal that acetate increases the adaptation speed of individual cells switching to the new nutrient. We conclude that the reuse of excreted acetate by E. coli facilitates metabolic adaptation by transiently replenishing central metabolite pools. This work identifies an unexpected role of acetate in the nutritional adaptation of E. coli , providing new insights into the physiological relevance of overflow metabolism.