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PMID: 10464196 Published · ppublish English Journal Article

The Cpx envelope stress response is controlled by amplification and feedback inhibition.

Journal of bacteriology ·Vol. 181 ·No. 17 ·1999-09-00 ·Pages 5263-72

Raivio TL, Popkin DL, Silhavy TJ

Abstract

In Escherichia coli, the Cpx two-component regulatory system activates expression of protein folding and degrading factors in response to misfolded proteins in the bacterial envelope (inner membrane, periplasm, and outer membrane). It is comprised of the histidine kinase CpxA and the response regulator CpxR. This response plays a role in protection from stresses, such as elevated pH, as well as in the biogenesis of virulence factors. Here, we show that the Cpx periplasmic stress response is subject to amplification and repression through positive and negative autofeedback mechanisms. Western blot and operon fusion analyses demonstrated that the cpxRA operon is autoactivated. Conditions that lead to elevated levels of phosphorylated CpxR cause a concomitant increase in transcription of cpxRA. Conversely, overproduction of CpxP, a small, Cpx-regulated protein of previously unknown function, represses the regulon and can block activation of the pathway. This repression is dependent on an intact CpxA sensing domain. The ability to autoactivate and then subsequently repress allows for a temporary amplification of the Cpx response that may be important in rescuing cells from transitory stresses and cueing the appropriately timed elaboration of virulence factors.

MeSH Terms
Bacterial Proteins/genetics Down-Regulation Escherichia coli/genetics Escherichia coli Proteins Feedback Gene Amplification Gene Expression Regulation, Bacterial Genes, Bacterial Membrane Proteins/genetics Operon Periplasm Protein Kinases/genetics Signal Transduction Transcriptional Activation
Chemicals
Bacterial Proteins CpxP protein, E coli CpxP protein, bacteria Escherichia coli Proteins Membrane Proteins CpxR protein, Bacteria Protein Kinases CpxA protein, E coli CpxA protein, bacteria
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Raivio T L
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Popkin D L
Silhavy T J
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.181.17.5263-5272.1999
Published
1999-09-00
Pages
5263-72
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC94031
Subset
IM
External Links
PubMed source DOI: 10.1128/JB.181.17.5263-5272.1999 PMC Full Text View journal details
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