TY - JOUR
T1 - Growth dependent heterogeneity in the DNA damage response in escherichia coli
AU - Jaramillo-Riveri, Sebastian
AU - Broughton, James
AU - McVey, Alexander
AU - Pilizota, Teuta
AU - Scott, Matthew
AU - El Karoui, Meriem
N1 - Funding Information:
We wish to thank Karolina Gaebe and Aleksandra Jarseva for performing preliminary characterization, and Nate Lord for supplying the strain used to amplify the mKate2 gene. We are grateful to David Leach and Benura Azeroglu for helpful discussions. We wish to thank Juan Carlos Arias Castro, Pascal Hersen, Dario Miroli, Eric Thorand and Filippo Menolascina for useful advice and discussions on the usage and design of the mother machine and microfluidics. The master production was performed in the Scottish Microelectronics Centre (SMC), the School of Engineering's small research facility, with the help of SMC’s staff. This work has been supported by a Wellcome Trust Investigator Award 205008/Z/16/Z (to M.E.K.), a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant 2016-03658 (to M.S.), the UKRI Synthetic Biology for Growth program and BBSRC/EPSRC/MRC funded Synthetic Biology Research Centre BB/M018040/1 (to T.P.), and two Darwin Trust of Edinburgh postgraduate studentships (to S.J.R. and J.B.).
Funding Information:
We wish to thank Karolina Gaebe and Aleksandra Jarseva for performing preliminary characterization, and Nate Lord for supplying the strain used to amplify the gene. We are grateful to David Leach and Benura Azeroglu for helpful discussions. We wish to thank Juan Carlos Arias Castro, Pascal Hersen, Dario Miroli, Eric Thorand and Filippo Menolascina for useful advice and discussions on the usage and design of the mother machine and microfluidics. The master production was performed in the Scottish Microelectronics Centre (SMC), the School of Engineering's small research facility, with the help of SMC’s staff. This work has been supported by a Wellcome Trust Investigator Award 205008/Z/16/Z (to M.E.K.), a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant 2016‐03658 (to M.S.), the UKRI Synthetic Biology for Growth program and BBSRC/EPSRC/MRC funded Synthetic Biology Research Centre BB/M018040/1 (to T.P.), and two Darwin Trust of Edinburgh postgraduate studentships (to S.J.R. and J.B.). mKate2
Publisher Copyright:
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2022/5/27
Y1 - 2022/5/27
N2 - In natural environments, bacteria are frequently exposed to sub-lethal levels of DNA damage, which leads to the induction of a stress response (the SOS response in Escherichia coli). Natural environments also vary in nutrient availability, resulting in distinct physiological changes in bacteria, which may have direct implications on their capacity to repair their chromosomes. Here, we evaluated the impact of varying the nutrient availability on the expression of the SOS response induced by chronic sub-lethal DNA damage in E. coli. We found heterogeneous expression of the SOS regulon at the single-cell level in all growth conditions. Surprisingly, we observed a larger fraction of high SOS-induced cells in slow growth as compared with fast growth, despite a higher rate of SOS induction in fast growth. The result can be explained by the dynamic balance between the rate of SOS induction and the division rates of cells exposed to DNA damage. Taken together, our data illustrate how cell division and physiology come together to produce growth-dependent heterogeneity in the DNA damage response.
AB - In natural environments, bacteria are frequently exposed to sub-lethal levels of DNA damage, which leads to the induction of a stress response (the SOS response in Escherichia coli). Natural environments also vary in nutrient availability, resulting in distinct physiological changes in bacteria, which may have direct implications on their capacity to repair their chromosomes. Here, we evaluated the impact of varying the nutrient availability on the expression of the SOS response induced by chronic sub-lethal DNA damage in E. coli. We found heterogeneous expression of the SOS regulon at the single-cell level in all growth conditions. Surprisingly, we observed a larger fraction of high SOS-induced cells in slow growth as compared with fast growth, despite a higher rate of SOS induction in fast growth. The result can be explained by the dynamic balance between the rate of SOS induction and the division rates of cells exposed to DNA damage. Taken together, our data illustrate how cell division and physiology come together to produce growth-dependent heterogeneity in the DNA damage response.
KW - DNA repair
KW - bacterial physiology
KW - single cell
U2 - 10.15252/msb.202110441
DO - 10.15252/msb.202110441
M3 - Article
VL - 18
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
M1 - e10441
ER -