Availability of the Molecular Switch XylR Controls Phenotypic Heterogeneity and Lag Duration during Escherichia coli Adaptation from Glucose to Xylose

The glucose-xylose metabolic transition is of growing interest as a model to explore cellular adaption since these molecules are the main substrates resulting from the deconstruction of lignocellulosic biomass. Here, we investigated the role of the XylR transcription factor in the length of the lag phases when the bacterium Escherichia coli needs to adapt from glucose- to xylose-based growth. First, a variety of lag times were observed when different strains of E. coli were switched from glucose to xylose. These lag times were shown to be controlled by XylR availability in the cells with no further effect on the growth rate on xylose. XylR titration provoked long lag times demonstrated to result from phenotypic heterogeneity during the switch from glucose to xylose, with a subpopulation unable to resume exponential growth, whereas the other subpopulation grew exponentially on xylose. A stochastic model was then constructed based on the assumption that XylR availability influences the probability of individual cells to switch to xylose growth. The model was used to understand how XylR behaves as a molecular switch determining the bistability set-up. This work shows that the length of lag phases in E. coli is controllable and reinforces the role of stochastic mechanism in cellular adaptation, paving the way for new strategies for the better use of sustainable carbon sources in bioeconomy.