Envelope Stress Responses: An Interconnected Safety Net

Abstract

The Escherichia coli cell envelope is a protective barrier at the frontline of interaction with the environment. Fidelity of envelope biogenesis must be monitored to establish and maintain a contiguous barrier. Indeed, the envelope must also be repaired and modified in response to environmental assaults. Envelope stress responses (ESRs) sense envelope damage or defects and alter the transcriptome to mitigate stress. We will review recent insights into stress sensing mechanisms of the σE and Cpx systems and the interaction of these ESRs. Small RNAs (sRNAs) are increasingly prominent regulators of the transcriptional response to stress. These fast-acting regulators also provide avenues for inter-ESR regulation that could be important when cells face multiple contemporaneous stresses, as is the case during infection.

The CpxR/CpxA system contributes to Salmonella gold‐resistance by controlling the GolS‐dependent gesABC transcription

“…CpxR is activated by conditions that disturb the cell envelope homeostasis and particularly the inner membrane, including alkaline pH, ethanol or metals such as Cu or Zn (Raivio, ; Delhaye et al ., ; Grabowicz and Silhavy, ; Pezza et al ., ; Surmann et al ., ). To verify the effective CpxR‐regulation of gesABC transcription, expression from a chromosomally encoded P ges‐lacZ reporter (Pontel et al ., ) was analyzed in the wild‐type strain as well as in mutants deleted in either cpxR or cpxA , or in both genes (Fig.…”

“…The CpxR/CpxA two‐component system modulates the transcription of more than fifty genes coding for chaperones, proteases and envelope‐associated complexes including several RND efflux pumps, many of them linked to metal homeostasis (Raivio, ; Grabowicz and Silhavy, ). In this work, we report that the Cpx system enhances the GolS‐dependent transcription of gesABC in response to Au ions, by binding to sequences located upstream from the GolS operator.…”

Stress Reduction, Bacterial Style

“…The Raivio group found, in earlier microarray studies, strong downregulation of two multiprotein IM complexes, NADH dehydrogenase and cytochrome bo 3 (17). In contrast to sigma factors, the CpxR response regulator can carry out direct repression, and in fact, this is the case for the nuo operon, encoding NADH dehydrogenase, and the cyo genes, encoding cytochrome bo 3 . Why are they downregulated?…”

How the Membrane Attack Complex Damages the Bacterial Cell Envelope and Kills Gram‐Negative Bacteria

“…This would require molecular interaction between the OM and the IM. [78,79] Finally, MAC-dependent OM damage may overstimulate stress responses in bacteria, [80,81] resulting in dysregulated cellular processes, vesiculation, [82][83][84] IM destabilization, and cell death. [69] It has been reported that the bacterial cell envelope contains regions in which the OM and IM are in close contact (so-called Bayer's junctions).…”