Toward a Spatially-Resolved Model of Metabolism in Dense Bacterial Colonies

Abstract

An individual cell's metabolic behavior is dependent on several factors, including both its protein-expression state as well as the availability of nutrients in its local environment. These two factors are not always independent; several transcription and translational regulatory systems allow the cell to respond to changes in its environment by adjusting the expression of metabolic enzymes, and thereby shifting its usage among different substrates. By integrating two methods for modeling whole cell phenomena, namely time-dependent reaction-diffusion master equation (RDME) sampling and steady-state flux-balance analysis (FBA), we are able to study how the competition for resources among bacteria in a dense colony gives rise to local micro-environments, and how these micro-environments in turn give rise to drastically different metabolic behaviors among cells. We find, in particular, that cooperative behavior can emerge among cells within the colony. Cells in the anaerobic interior of the colony partially metabolize glucose to acetate, which can then be taken up and metabolized by cells on the more aerobic periphery of the colony.