RT Journal Article
SR Electronic
T1 History-Dependent Physiological Adaptation to Lethal Genetic Modification under Antibiotic Exposure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.05.459045
DO 10.1101/2021.09.05.459045
A1 Yuta Koganezawa
A1 Miki Umetani
A1 Moritoshi Sato
A1 Yuichi Wakamoto
YR 2021
UL http://biorxiv.org/content/early/2021/09/06/2021.09.05.459045.abstract
AB Genetic modifications, such as gene deletion and mutations, could lead to significant changes in physiological states or even cell death. Bacterial cells can adapt to diverse external stresses, such as antibiotic exposure, but can they also adapt to detrimental genetic modification? To address this issue, we visualized the response of individual Escherichia coli cells to deletion of the antibiotic resistance gene under chloramphenicol (Cp) exposure, combining the light-inducible genetic recombination and microfluidic long-term single-cell tracking. We found that a significant fraction (∼ 40%) of resistance-gene-deleted cells demonstrated a gradual restoration of growth and stably proliferated under continuous Cp exposure without additional mutations. Such physiological adaptation to genetic modification was not observed when the deletion was introduced in 10 h or more advance before Cp exposure. Resistance gene deletion under Cp exposure disrupted the stoichiometric balance of ribosomal large and small subunit proteins (RplS and RpsB). However, the balance was gradually recovered in the cell lineages with restored growth. These results demonstrate that bacterial cells can adapt even to lethal genetic modifications by plastically gaining physiological resistance. However, the access to the resistance states is limited by the environmental histories and the timings of genetic modification.Competing Interest StatementThe authors have declared no competing interest.