Survival of ampicillin-treated uropathogenic Escherichia coli is independent of single-cell growth rates

The refractoriness of persistent infections to antibiotics necessitates lengthy treatment regimens to prevent therapeutic failures and relapses. Persistence has been attributed to entry of a small fraction of bacterial cells into a slowly growing or non-growing physiological state, which is thought to protect them against antibiotics targeting growth-related processes. However, these conclusions are largely based on studies conducted with lab-adapted strains carrying mutations that confer abnormally high levels of persistence. Here, we perform single-cell studies of ampicillin-mediated killing and persistence in a clinical isolate of uropathogenic Escherichia coli (UPEC). We show that the majority of surviving cells are growing and dividing normally at the time of ampicillin exposure. Conversely, we find that the majority of non-growing cells are readily killed by ampicillin exposure. These findings challenge the widespread assumption that bacterial dormancy and persistence are inextricably linked.