Observation of universal ageing dynamics in antibiotic persistence

Yoav Kaplan, Shaked Reich, Elyaqim Oster, Shani Maoz, Irit Levin-Reisman, Irine Ronin, Orit Gefen, Oded Agam () and Nathalie Q. Balaban ()
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Yoav Kaplan: The Hebrew University of Jerusalem
Shaked Reich: The Hebrew University of Jerusalem
Elyaqim Oster: The Hebrew University of Jerusalem
Shani Maoz: The Hebrew University of Jerusalem
Irit Levin-Reisman: The Hebrew University of Jerusalem
Irine Ronin: The Hebrew University of Jerusalem
Orit Gefen: The Hebrew University of Jerusalem
Oded Agam: The Hebrew University of Jerusalem
Nathalie Q. Balaban: The Hebrew University of Jerusalem

Nature, 2021, vol. 600, issue 7888, 290-294

Abstract: Abstract Stress responses allow cells to adapt to changes in external conditions by activating specific pathways1. Here we investigate the dynamics of single cells that were subjected to acute stress that is too strong for a regulated response but not lethal. We show that when the growth of bacteria is arrested by acute transient exposure to strong inhibitors, the statistics of their regrowth dynamics can be predicted by a model for the cellular network that ignores most of the details of the underlying molecular interactions. We observed that the same stress, applied either abruptly or gradually, can lead to totally different recovery dynamics. By measuring the regrowth dynamics after stress exposure on thousands of cells, we show that the model can predict the outcome of antibiotic persistence measurements. Our results may account for the ubiquitous antibiotic persistence phenotype2, as well as for the difficulty in attempts to link it to specific genes3. More generally, our approach suggests that two different cellular states can be observed under stress: a regulated state, which prepares cells for fast recovery, and a disrupted cellular state due to acute stress, with slow and heterogeneous recovery dynamics. The disrupted state may be described by general properties of large random networks rather than by specific pathway activation. Better understanding of the disrupted state could shed new light on the survival and evolution of cells under stress.

Date: 2021
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DOI: 10.1038/s41586-021-04114-w

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