Slow trajectories generate divergent cell fates following antibiotic stress

Abstract

Single-cell microfluidic experiments have shown that upon abrupt exposures to antibiotics, genetically homogeneous microbial populations undergo divergent cell fates. The mechanism underlying this divergence is not clear and in particular, the emergence of a range of distinct slow-growing phenotypes cannot be explained by models relying on bistability alone. Here, we propose a model for gene expression and growth dynamics during antibiotic exposures, which is informed by well-known scaling relations connecting proteome allocation and cell growth. In our model, resources available for transcription and translation of resistance genes act like generalized momenta and their initial variation is predictive of cell fate. Our model reproduces key experimental observations, including the prediction of specific phenotypes and a critical threshold in initial resource allocation that predicts cell survival. These results offer an alternative mechanism for the emergence of phenotypic diversity where slow cell growth effectively stabilizes cellular states along the trajectory that are far from the final stable states predicted by fixed points.