Envelope Stress Responses in Escherichia coli

Summary

The cell envelope of Escherichia coli is a multilayered barrier that separates the cytoplasm from a fluctuating environment. It comprises the inner membrane, the peptidoglycan layer and the outer membrane, each of which is vulnerable to physical, chemical and biological insults. Envelope stress responses (ESRs) are specialised regulatory networks that detect perturbations—such as misfolded proteins, antimicrobial peptides, osmotic shifts or cell‐wall damage—and initiate adaptive programmes to restore integrity. Key ESR pathways include the σE (RpoE) extracytoplasmic sigma factor system, the CpxA/CpxR two‐component module, the phage shock protein (Psp) response, the Bae system and the Rcs phosphorelay. Activation of these circuits leads to the upregulation of chaperones, proteases, lipoprotein assembly factors and cell-wall-remodelling enzymes. Through coordinated regulation of transcription, protein quality control and envelope biogenesis, ESRs maintain envelope homeostasis, contribute to antibiotic tolerance and shape interactions with host tissues and other microbes.

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Envelope Stress Responses in Escherichia coli publication trend

The graph below shows the total number of articles in envelope stress responses in escherichia coli across all publications each year (not limited to Nature Index journals).

Technical terms

Envelope Stress Response (ESR): A set of signal transduction pathways that detect damage to the cell envelope and initiate gene expression programmes to restore envelope integrity.

σE (RpoE): An extracytoplasmic function sigma factor that directs RNA polymerase to promoters of genes involved in outer‐membrane and periplasmic protein folding and assembly.

Cpx two-component system: A membrane-associated sensor kinase (CpxA) and response regulator (CpxR) pair that monitors misfolded proteins in the periplasm and adjusts expression of chaperones and quality-control factors.

Regulon: A group of genes or operons controlled by a common regulatory protein, such as σE or CpxR, that coordinate a specific stress response.

Periplasm: The gel-like compartment between the inner and outer membranes of Gram-negative bacteria where many envelope proteins fold, assemble and are quality-checked.

Proteolytic cascade: A sequence of regulated protease activations (e.g. DegS and RseP in the σE pathway) that liberate sigma factors or regulators to initiate transcriptional responses.

References

  1. Regulatory role of the Cpx ESR in bacterial behaviours. Virulence (2024).
  2. Are envelope stress responses essential for persistence to β-lactams in Escherichia coli?. Antimicrobial Agents and Chemotherapy (2023).

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