title: The response to extracytoplasmic stress in Escherichia coli is controlled by partially overlapping pathways.
abstract: The activity of the alternate sigma-factor sigmaE of Escherichia coli is induced by several stressors that lead to the extracytoplasmic accumulation of misfolded or unfolded protein. The sigmaE regulon contains several genes, including that encoding the periplasmic protease DegP, whose products are thought to be required for maintaining the integrity of the cell envelope because cells lacking sigmaE are sensitive to elevated temperature and hydrophobic agents. Selection of multicopy suppressors of the temperature-sensitive phenotype of cells lacking sigmaE revealed that overexpression of the lipoprotein NlpE restored high temperature growth to these cells. Overexpression of NlpE has been shown previously to induce DegP synthesis by activating the Cpx two-component signal transduction pathway, and suppression of the temperature-sensitive phenotype by NlpE was found to be dependent on the Cpx proteins. In addition, a constitutively active form of the CpxA sensor/kinase also fully suppressed the temperature-sensitive defect of cells lacking sigmaE. DegP was found to be necessary, but not sufficient, for suppression. Activation of the Cpx pathway has also been shown to alleviate the toxicity of several LamB mutant proteins. Together, these results reveal the existence of two partially overlapping regulatory systems involved in the response to extracytoplasmic stress in E. coli.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, USA.
authors.forename: L
authors.initials: L
authors.lastname: Connolly
authors.forename: A
authors.initials: A
authors.lastname: De Las Penas
authors.forename: B M
authors.initials: BM
authors.lastname: Alba
authors.forename: C A
authors.initials: CA
authors.lastname: Gross
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005798:Genes, Bacterial / Q000502:physiology; D016153:Genes, Suppressor / Q000235:genetics; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response / Q000235:genetics*; D008074:Lipoproteins / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D033903:Periplasmic Proteins; D010641:Phenotype; D011494:Protein Kinases; D018085:Regulon / Q000502:physiology; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008074:Lipoproteins; C095021:NlpE protein, E coli; D033903:Periplasmic Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C063202:sporulation-specific sigma factors; D011494:Protein Kinases; C490475:CpxA protein, E coli; C092472:CpxA protein, bacteria; C061682:DegP protease; D012697:Serine Endopeptidases