(795a) Attenuated Bistability in Bacterial Sugar Utilization

Sugar utilization in bacteria has served as a powerful model to understand gene regulation and the emergence of single-cell behaviors. The prototypic example is the ‘all-or-none’ response in lactose utilization, where cells are either uninduced or fully induced in the presence of a lactose analog. The utilization of lactose and other sugars predominantly has been studied in the absence of sugar catabolism--either through the use of stable sugar analogs or deletion of the catabolic genes. In contrast, natural utilization pathways inherently catabolize the sugar as part of the response. This discrepancy begs the question: how does sugar catabolism shape the response of individual cells, especially across the myriad of sugar utilization pathways present in bacteria?

Using a combination of transcriptional reporters and stochastic modeling, we are investigating the single-cell response of representative sugar utilization pathways in Escherichia coli. Our results indicate that examined pathways exhibit ranging responses that can be generally described as attenuated bistability. This response is bimodal yet exhibits reduced hysteresis in comparison to bistable systems. Deletion of the catabolic genes reverts the exhibited response to an ‘all-or-none’ response with greater hysteresis, in line with the behavior of pathways lacking sugar catabolism. Mathematical modeling predicted these same responses and indicated the importance of the balance between the induction and activity of the transporters and catabolic enzymes. Our overall results suggest that bacterial sugar utilization pathways exhibit complex, single-cell responses, potentially representing common foraging strategies in sparse and unpredictable environments. With continued efforts, insights into these responses may reshape our fundamental understanding of how microorganisms utilize nutrients in their surrounding environment.