A universal trade-off between growth and lag in fluctuating environments

Area of Science:

• Microbiology
• Systems Biology
• Biophysics

Background:

• Bacterial cell growth rate is vital for fitness and resource allocation.
• Environmental conditions and physiological adaptation also influence bacterial objectives.
• Optimizing growth and adaptability simultaneously presents a challenge due to inherent trade-offs.

Purpose of the Study:

• To investigate the trade-off between steady-state growth rate and physiological adaptability in Escherichia coli.
• To understand the mechanisms behind metabolic transition lags in bacteria.
• To model and predict the universality of growth-adaptability trade-offs.

Main Methods:

• Experimental nutrient shifts in Escherichia coli cultures (e.g., glucose to acetate).
• Metabolomic analysis to identify key metabolite changes during transitions.
• Development of a sequential flux limitation model.
• Experimental validation across different nutrient shifts and microbial species.

Main Results:

• A trade-off exists between steady-state growth rate and physiological adaptability in E. coli.
• Long metabolic transition lags are caused by key metabolite depletion after central carbon flux reversal.
• The sequential flux limitation model accurately explains the observed trade-off.
• Model predictions for universal trade-offs were experimentally validated.

Conclusions:

• Bacterial growth and adaptability are subject to fundamental trade-offs.
• Metabolite dynamics and opposing enzyme requirements (glycolysis vs. gluconeogenesis) drive these trade-offs.
• These findings have implications for understanding microbial fitness and adaptation across diverse species.