Single-cell dynamics reveals sustained growth during diauxic shifts

Area of Science:

• Microbiology
• Systems Biology
• Molecular Genetics

Background:

• Gene regulatory stochasticity is well-documented, but its impact on cellular growth and fitness remains less understood.
• The diauxic shift, involving a switch from glucose to lactose metabolism in *E. coli*, typically exhibits a growth arrest phase (lag phase) in bulk cultures.

Purpose of the Study:

• To investigate the individual cell growth dynamics and gene expression during the glucose-to-lactose metabolic shift in *E. coli*.
• To determine the role of stochastic gene expression in mediating cellular responses to nutrient availability and growth.
• To assess the selective advantages conferred by suppressing the growth lag phase.

Main Methods:

• Utilized a single-cell assay in a microfluidic device to track *E. coli* cell elongation and lac operon expression at minute resolution.
• Developed and employed a stochastic molecular model integrating nutrient concentration, lac expression, and growth rate dependencies.
• Compared individual cell behaviors with bulk culture observations.

Main Results:

• Observed that while most cells exhibit a growth arrest upon glucose depletion, a significant fraction maintains high elongation rates without a lag phase.
• Demonstrated a non-linear relationship between lac expression levels and growth rate, with partial induction sufficient for near-maximal growth.
• The stochastic molecular model accurately replicated observed cell switching distributions and growth dynamics.

Conclusions:

• A growth arrest is not an obligatory event during the diauxic shift, contrary to bulk observations.
• Regulatory stochasticity plays a crucial role in cellular growth, survival, and adaptation, particularly under nutrient-limited conditions.
• The ability to suppress the lag phase provides a selective advantage, highlighting the importance of considering individual cell variability.