Intercellular interaction mechanisms promote diversity in intracellular ATP concentration in Escherichia coli populations

Abstract

AbstractIn fluctuating environments, many microorganisms acquire phenotypic heterogeneity as a survival tactic to increase the likelihood of survival of the overall population. One example of this interindividual heterogeneity is the diversity of ATP concentration among members ofEscherichia colipopulations under glucose deprivation. Despite the importance of such environmentally driven phenotypic heterogeneity, how the differences in intracellular ATP concentration emerge among individualE. coliorganisms is unknown. In this study, we focused on the mechanism through which individualE. coliachieve high intracellular ATP concentrations. First, we measured the ATP retained byE. coliover time when cultured at low (0.1 mM) and control (22.2 mM) concentrations of glucose and obtained the chronological change in ATP concentrations. Then, by comparing these chronological change of ATP concentrations and analyzing whether stochastic state transitions, periodic oscillations, cellular age, and intercellular communication—which have been reported as molecular biological mechanisms for generating interindividual heterogeneity—are involved, we showed that the appearance of high ATP-holding individuals observed amongE. colican be explained only by intercellular transmission. By performing metabolomic analysis of post-culture medium, we revealed a significant increase in the ATP, especially at low glucose, and that the number ofE. colithat retain significantly higher ATP can be controlled by adding large amounts of ATP to the medium, even in populations cultured under control glucose concentrations. These results reveal for the first time that ATP-mediated intercellular transmission enables some individuals inE. colipopulations grown at low glucose to retain large amounts of ATP.