Seminar: "Glycerol-Driven Energy Metabolism Sustains Antibiotic Tolerance in Stationary-Phase Escherichia coli" - Mehmet Orman
Mehmet Orman, Ph.D.
Associate Professor
University of Wisconsin-Madison
A major gap remains in our understanding of how bacterial metabolism is rewired as cells enter a persistent, antibiotic-tolerant state, and which metabolic pathways become essential for persister survival. We study Escherichia coli persister cells that arise in late stationary phase, a physiological state marked by nutrient limitation, high cell density, and extensive cellular remodeling. We previously found that the global regulator Crp/cAMP redirects persister metabolism away from biosynthesis and toward oxidative phosphorylation. Although persister cells exhibit lower overall metabolic activity than exponentially growing cells, our data indicates that their survival still depends on active energy metabolism. Integrated genomic, metabolomic, proteomic, and genetic analyses consistently highlight the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and ATP synthase as core determinants of persister maintenance.
In this talk, I will present evidence that lipid-derived glycerol functions as a key endogenous carbon source that feeds central metabolism to sustain the proton motive force and basal energy balance in stationary-phase persisters. I will discuss how disrupting glycerol catabolism or perturbing the TCA cycle rewires stress responses, alters proteostasis, and compromises energy metabolism, thereby reducing persister survival. I will also describe single-cell imaging results revealing distinctive cytological features of stationary-phase persisters and how these features are modified in glycerol-utilization and TCA-cycle mutants. Together, these findings support a model in which persister cells are metabolically active, sustained by selective endogenous carbon flux, likely linked to phospholipid recycling, and suggest new strategies for targeting persistence by disrupting internal energy supply.