History-dependent physiological adaptation to lethal genetic modification under antibiotic exposure

Area of Science:

• Microbiology
• Genetics
• Cell Biology

Background:

• Bacterial cells exhibit remarkable adaptability to environmental stresses, including antibiotics.
• The capacity of bacteria to adapt to detrimental genetic modifications remains less understood.
• Understanding adaptation to genetic loss is crucial for predicting bacterial evolution.

Purpose of the Study:

• To investigate the adaptive potential of individual *Escherichia coli* cells to the deletion of an antibiotic resistance gene under antibiotic pressure.
• To determine if bacteria can overcome lethal genetic modifications through physiological adaptation.
• To explore the influence of timing between genetic modification and environmental stress on adaptation.

Main Methods:

• Utilized light-inducible genetic recombination for precise gene deletion in *E. coli*.
• Employed microfluidic devices for long-term single-cell tracking and observation.
• Analyzed ribosomal protein stoichiometry (RplS and RpsB) to assess cellular adaptation.

Main Results:

• Approximately 40% of cells lacking the resistance gene adapted and restored growth under continuous chloramphenicol (Cp) exposure.
• Adaptation was observed only when gene deletion occurred concurrently with Cp exposure, not prior.
• Gene deletion initially disrupted ribosomal protein balance, which was restored in adapting cell lineages.

Conclusions:

• Bacterial cells can plastically acquire physiological resistance to adapt to lethal genetic modifications.
• The ability to adapt is contingent upon the environmental history and the temporal relationship between genetic alteration and stress exposure.
• This study highlights the dynamic interplay between genetic changes and physiological plasticity in bacterial adaptation.