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

Abstract

Antibiotic treatment failure is often driven by non-genetic survival mechanisms such as tolerance and persistence, but how beta-lactams affect cells resuscitating from dormancy has remained unclear. Using Hi-DFA, a high-throughput single-cell microfluidic imaging platform, this work shows that many resuscitating cells transiently slow their growth and thereby survive beta-lactam exposure.

This transiently tolerant phenotype is much less common in unstressed, exponentially growing cells, indicating that prior starvation history predisposes cells to it. Simulations and population modelling further suggest that these transiently tolerant cells, rather than classical starvation-triggered persisters, can dominate rapid regrowth after treatment under clinically relevant dosing conditions.

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." bioRxiv.
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