Abstract
Inducible utilization pathways reflect widespread microbial strategies to uptake and consume sugars from the environment. Despite their broad importance and extensive characterization, little is known how these pathways naturally respond to their inducing sugar in individual cells. Here, we performed single-cell analyses to probe the behaviour of representative pathways in the model bacterium Escherichia coli. We observed diverse single-cell behaviours, including uniform responses (d-lactose, d-galactose, N-acetylglucosamine, N-acetylneuraminic acid), 'all-or-none' responses (d-xylose, l-rhamnose) and complex combinations thereof (l-arabinose, d-gluconate). Mathematical modelling and probing of genetically modified pathways revealed that the simple framework underlying these pathways - inducible transport and inducible catabolism - could give rise to most of these behaviours. Sugar catabolism was also an important feature, as disruption of catabolism eliminated tunable induction as well as enhanced memory of previous conditions. For instance, disruption of catabolism in pathways that respond to endogenously synthesized sugars led to full pathway induction even in the absence of exogenous sugar. Our findings demonstrate the remarkable flexibility of this simple biological framework, with direct implications for environmental adaptation and the engineering of synthetic utilization pathways as titratable expression systems and for metabolic engineering.