Metabolic flux regulates growth transitions and antibiotic tolerance in uropathogenic Escherichia coli .

Uropathogenic (UPEC) are the leading cause of urinary tract infections (UTIs). Upon invasion into bladder epithelial cells, UPEC establish quiescent intracellular reservoirs that may lead to antibiotic tolerance and recurrent UTIs. Here, we demonstrate using an in vitro system that quiescent UPEC cells are tolerant to ampicillin and have decreased metabolism characterized by succinyl-CoA limitation. We identify the global regulator the IHF complex and the cell division protein ZapE as critical regulators of quiescence and antibiotic tolerance. Lastly, we show ZapE interacts with components of both the cell division machinery and the TCA cycle, and this interaction is conserved in non-pathogenic , establishing a novel link between cell division and metabolism.