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. 1997 Feb;179(4):1029–1034. doi: 10.1128/jb.179.4.1029-1034.1997

The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine.

E Mileykovskaya 1, W Dowhan 1
PMCID: PMC178794  PMID: 9023180

Abstract

The CpxA-CpxR two-component signal transduction pathway of Escherichia coli was studied in a mutant (pss-93) lacking phosphatidylethanolamine (PE). Several properties of this mutant are comparable to phenotypes of cpxA point mutants, indicating that this two-component pathway is activated in PE-deficient cells. In contrast to point mutants, cpx operon null mutants have a wild-type phenotype. By use of this information, a cpx operon null allele was introduced into a pss-93 mutant. Certain altered properties of PE-deficient mutants, which were consistent with activation of the Cpx pathway, returned to the wild-type phenotype, namely, active accumulation of proline and thiomethyl-beta-D-galactopyranoside was partially restored to wild-type levels, increased resistance to amikacin returned to wild-type sensitivity, and high levels of degP expression returned to repressed wild-type levels. Elevated levels of acetyl phosphate and nlpE gene product can result in activation of the Cpx pathway. However, inactivation of the nlpE gene or mutations eliminating the ability to make acetyl phosphate did not alter the high level of degP expression in pss-93 mutants. We propose that the lack of PE results in an alteration in cell envelope structure or physical properties, leading to direct activation of the Cpx pathway.

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Selected References

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  1. Albin R., Silverman P. M. Physical and genetic structure of the glpK-cpxA interval of the Escherichia coli K-12 chromosome. Mol Gen Genet. 1984;197(2):261–271. doi: 10.1007/BF00330972. [DOI] [PubMed] [Google Scholar]
  2. Bass S., Gu Q., Christen A. Multicopy suppressors of prc mutant Escherichia coli include two HtrA (DegP) protease homologs (HhoAB), DksA, and a truncated R1pA. J Bacteriol. 1996 Feb;178(4):1154–1161. doi: 10.1128/jb.178.4.1154-1161.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bibi E., Kaback H. R. In vivo expression of the lacY gene in two segments leads to functional lac permease. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4325–4329. doi: 10.1073/pnas.87.11.4325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bogdanov M., Dowhan W. Phosphatidylethanolamine is required for in vivo function of the membrane-associated lactose permease of Escherichia coli. J Biol Chem. 1995 Jan 13;270(2):732–739. doi: 10.1074/jbc.270.2.732. [DOI] [PubMed] [Google Scholar]
  5. Bogdanov M., Sun J., Kaback H. R., Dowhan W. A phospholipid acts as a chaperone in assembly of a membrane transport protein. J Biol Chem. 1996 May 17;271(20):11615–11618. doi: 10.1074/jbc.271.20.11615. [DOI] [PubMed] [Google Scholar]
  6. Danese P. N., Snyder W. B., Cosma C. L., Davis L. J., Silhavy T. J. The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 1995 Feb 15;9(4):387–398. doi: 10.1101/gad.9.4.387. [DOI] [PubMed] [Google Scholar]
  7. DeChavigny A., Heacock P. N., Dowhan W. Sequence and inactivation of the pss gene of Escherichia coli. Phosphatidylethanolamine may not be essential for cell viability. J Biol Chem. 1991 Mar 15;266(8):5323–5332. [PubMed] [Google Scholar]
  8. Dong J., Iuchi S., Kwan H. S., Lu Z., Lin E. C. The deduced amino-acid sequence of the cloned cpxR gene suggests the protein is the cognate regulator for the membrane sensor, CpxA, in a two-component signal transduction system of Escherichia coli. Gene. 1993 Dec 22;136(1-2):227–230. doi: 10.1016/0378-1119(93)90469-j. [DOI] [PubMed] [Google Scholar]
  9. Escribá P. V., Sastre M., García-Sevilla J. A. Disruption of cellular signaling pathways by daunomycin through destabilization of nonlamellar membrane structures. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7595–7599. doi: 10.1073/pnas.92.16.7595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Everest P., Frankel G., Li J., Lund P., Chatfield S., Dougan G. Expression of LacZ from the htrA, nirB and groE promoters in a Salmonella vaccine strain: influence of growth in mammalian cells. FEMS Microbiol Lett. 1995 Feb 1;126(1):97–101. doi: 10.1111/j.1574-6968.1995.tb07398.x. [DOI] [PubMed] [Google Scholar]
  11. Gibson N. J., Brown M. F. Lipid headgroup and acyl chain composition modulate the MI-MII equilibrium of rhodopsin in recombinant membranes. Biochemistry. 1993 Mar 9;32(9):2438–2454. doi: 10.1021/bi00060a040. [DOI] [PubMed] [Google Scholar]
  12. Hasin M., Kennedy E. P. Role of phosphatidylethanolamine in the biosynthesis of pyrophosphoethanolamine residues in the lipopolysaccharide of Escherichia coli. J Biol Chem. 1982 Nov 10;257(21):12475–12477. [PubMed] [Google Scholar]
  13. Johnson K., Charles I., Dougan G., Pickard D., O'Gaora P., Costa G., Ali T., Miller I., Hormaeche C. The role of a stress-response protein in Salmonella typhimurium virulence. Mol Microbiol. 1991 Feb;5(2):401–407. doi: 10.1111/j.1365-2958.1991.tb02122.x. [DOI] [PubMed] [Google Scholar]
  14. Kim S. H. "Frozen" dynamic dimer model for transmembrane signaling in bacterial chemotaxis receptors. Protein Sci. 1994 Feb;3(2):159–165. doi: 10.1002/pro.5560030201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Koshland D. E., Jr Chemotaxis as a model second-messenger system. Biochemistry. 1988 Aug 9;27(16):5829–5834. doi: 10.1021/bi00416a001. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lipinska B., Zylicz M., Georgopoulos C. The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase. J Bacteriol. 1990 Apr;172(4):1791–1797. doi: 10.1128/jb.172.4.1791-1797.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lukat G. S., McCleary W. R., Stock A. M., Stock J. B. Phosphorylation of bacterial response regulator proteins by low molecular weight phospho-donors. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):718–722. doi: 10.1073/pnas.89.2.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McCallum C. D., Epand R. M. Insulin receptor autophosphorylation and signaling is altered by modulation of membrane physical properties. Biochemistry. 1995 Feb 14;34(6):1815–1824. doi: 10.1021/bi00006a001. [DOI] [PubMed] [Google Scholar]
  20. McCleary W. R., Stock J. B., Ninfa A. J. Is acetyl phosphate a global signal in Escherichia coli? J Bacteriol. 1993 May;175(10):2793–2798. doi: 10.1128/jb.175.10.2793-2798.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McEwen J., Silverman P. M. Mutations in genes cpxA and cpxB alter the protein composition of Escherichia coli inner and outer membranes. J Bacteriol. 1982 Sep;151(3):1553–1559. doi: 10.1128/jb.151.3.1553-1559.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McEwen J., Silverman P. Chromosomal mutations of Escherichia coli that alter expression of conjugative plasmid functions. Proc Natl Acad Sci U S A. 1980 Jan;77(1):513–517. doi: 10.1073/pnas.77.1.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McEwen J., Silverman P. Genetic analysis of Escherichia coli K-12 chromosomal mutants defective in expression of F-plasmid functions: identification of genes cpxA and cpxB. J Bacteriol. 1980 Oct;144(1):60–67. doi: 10.1128/jb.144.1.60-67.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McEwen J., Silverman P. Mutations in genes cpxA and cpxB of Escherichia coli K-12 cause a defect in isoleucine and valine syntheses. J Bacteriol. 1980 Oct;144(1):68–73. doi: 10.1128/jb.144.1.68-73.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mileykovskaya E. I., Dowhan W. Alterations in the electron transfer chain in mutant strains of Escherichia coli lacking phosphatidylethanolamine. J Biol Chem. 1993 Nov 25;268(33):24824–24831. [PubMed] [Google Scholar]
  26. Pertinhez T. A., Nakaie C. R., Carvalho R. S., Paiva A. C., Tabak M., Toma F., Schreier S. Conformational changes upon binding of a receptor loop to lipid structures: possible role in signal transduction. FEBS Lett. 1995 Nov 20;375(3):239–242. doi: 10.1016/0014-5793(95)01222-z. [DOI] [PubMed] [Google Scholar]
  27. Raetz C. R., Foulds J. Envelope composition and antibiotic hypersensitivity of Escherichia coli mutants defective in phosphatidylserine synthetase. J Biol Chem. 1977 Aug 25;252(16):5911–5915. [PubMed] [Google Scholar]
  28. Rainwater S., Silverman P. M. The Cpx proteins of Escherichia coli K-12: evidence that cpxA, ecfB, ssd, and eup mutations all identify the same gene. J Bacteriol. 1990 May;172(5):2456–2461. doi: 10.1128/jb.172.5.2456-2461.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schnaitman C. A., Klena J. D. Genetics of lipopolysaccharide biosynthesis in enteric bacteria. Microbiol Rev. 1993 Sep;57(3):655–682. doi: 10.1128/mr.57.3.655-682.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Silverman P. M. Gene cpxA is a new addition to the linkage map of Escherichia coli K-12. J Bacteriol. 1982 Apr;150(1):425–428. doi: 10.1128/jb.150.1.425-428.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Snyder W. B., Davis L. J., Danese P. N., Cosma C. L., Silhavy T. J. Overproduction of NlpE, a new outer membrane lipoprotein, suppresses the toxicity of periplasmic LacZ by activation of the Cpx signal transduction pathway. J Bacteriol. 1995 Aug;177(15):4216–4223. doi: 10.1128/jb.177.15.4216-4223.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Strauch K. L., Johnson K., Beckwith J. Characterization of degP, a gene required for proteolysis in the cell envelope and essential for growth of Escherichia coli at high temperature. J Bacteriol. 1989 May;171(5):2689–2696. doi: 10.1128/jb.171.5.2689-2696.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Su H. S., Lang B. F., Newman E. B. L-serine degradation in Escherichia coli K-12: cloning and sequencing of the sdaA gene. J Bacteriol. 1989 Sep;171(9):5095–5102. doi: 10.1128/jb.171.9.5095-5102.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wanner B. L., Wilmes-Riesenberg M. R. Involvement of phosphotransacetylase, acetate kinase, and acetyl phosphate synthesis in control of the phosphate regulon in Escherichia coli. J Bacteriol. 1992 Apr;174(7):2124–2130. doi: 10.1128/jb.174.7.2124-2130.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weber R. F., Silverman P. M. The cpx proteins of Escherichia coli K12. Structure of the cpxA polypeptide as an inner membrane component. J Mol Biol. 1988 Sep 20;203(2):467–478. doi: 10.1016/0022-2836(88)90013-7. [DOI] [PubMed] [Google Scholar]

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