System-wide increased variability in E.coli in response to acute stress

Bacterial stress responses are usually characterized by a highly coordinated up-regulation of stress response genes. However, in the case of antibiotic tolerance, conflicting evidence points to different sets of genes. We have recently shown that under many types of acute stress, bacteria arrest their growth and enter a disrupted state, characterized by a broad lag time distribution upon recovery. Our understanding of this response as a strong random perturbation of the cell, has led us to predict that such disrupted cells will also be variable in other cellular observables.

In this study, we compare growth-arrested bacteria in the disrupted state to bacteria that arrest their growth through a coordinated stress response. We study the variability of these two types of growth arrested bacteria using RNAseq, microfluidics microscopy and bulk fluorescence measurements. The results show a significantly increased variability of disrupted bacteria in all measured parameters.

Our work shows that not all stress responses can be described as an orchestrated implementation of a cellular program. Rather, disrupted bacteria go into a disorganized state that does not fit the paradigm of a coordinated stress response.