Speaker
Description
Bacteria exhibit remarkable phenotypic heterogeneity upon antibiotic exposure, induced by complex feedback mechanisms mediated by interactions between drug action, metabolism, gene regulation, and expression of resistance. However, how global transcriptional programs are rewired under drug stress in these different phenotypes remains poorly understood. In Escherichia coli, exposure to the translation inhibitor tetracycline was shown to produce distinct phenotypes with a range of growth rates, whose underlying transcriptional states have not been fully characterized. Here, we use RNA sequencing across nutrient and drug conditions to show that increasing tetracycline concentration leads to a progressive breakdown of transcriptional organization and the emergence of a disordered gene expression state. We find that exposure to intermediate tetracycline concentrations induce coordinated transcriptional changes consistent with the maintenance of homeostasis under the drug. In contrast, high drug levels trigger widespread dysregulation marked by increased transcriptional entropy, and the upregulation of stress and resistance functions at the expense of metabolism and growth. This work combines environmental perturbations with bulk transcriptomics to develop models explaining the progression of heterogeneous cellular states, providing insight into how bacteria persist in growth-limited, clinically relevant conditions.
