Trade-off between resistance and persistence in high cell density cultures

Area of Science:

• Microbiology and Systems Biology
• Biotechnology and Bioprocessing

Background:

• High cell density bacterial growth is crucial in infections, microbiomes, and biomanufacturing.
• Understanding transcriptional regulation under stress in dense cultures is limited.

Purpose of the Study:

• To characterize transcriptional dynamics in high-density *Escherichia coli* cultures.
• To identify regulatory strategies balancing growth and survival under stress.

Main Methods:

• Utilized controlled culturing systems for wild-type and engineered *E. coli* to reach high cell densities (50-80 gcdw L⁻¹).
• Employed knowledge-enriched, machine-learning-based analytics on over 470 transcriptomic samples.
• Analyzed gene expression patterns to identify stress-related stimulons.

Main Results:

• Identified distinct stress-related gene expression patterns indicating a trade-off between resistance and persistence.
• Observed growth arrests in high-density cultures linked to this trade-off.
• Found that resource reallocation from resistance to maintenance disrupts cellular homeostasis.

Conclusions:

• High-density bacterial physiology involves programmed persistence phenotypes as hidden transcriptional states.
• The resistance-persistence trade-off is a fundamental mechanism in dense bacterial populations.
• Findings impact genome editing strategies for resilient strains in biomanufacturing and infection models.