Stress History Establishes a Transient Tolerant State That Shapes Antibiotic Survival Upon Resuscitation

Abstract

Using Hi-DFA, a high-throughput microfluidic platform for single-cell fate tracking, we measured resuscitating bacteria at scale and found that a substantial fraction temporarily slow their growth. That transient slowdown improves survival when beta-lactams are introduced, and it is much more common after prior starvation than in unstressed exponential cells.

Simulated in vitro pharmacokinetic profiles and a population dynamics model suggest that transiently tolerant cells, rather than classical starvation-induced persisters, can be the main drivers of rapid regrowth after treatment. The result defines a stress-history-dependent route to antibiotic survival with direct relevance for dosing strategy.

Recommended citation: Abbott, K., Hardo, G., Li, R., Bradley, J., Zarkan, A., Bakshi, S. (2026). "Stress History Establishes a Transient Tolerant State That Shapes Antibiotic Survival Upon Resuscitation." Advanced Science e21993.
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