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Chapter 5 : The Cpx Envelope Stress Response

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Abstract:

This chapter summarizes studies that led to identification and characterization of the Cpx envelope stress response and highlights recent work that hints at a diverse range of Cpx-influenced cellular phenotypes. Silverman and colleagues provided the kernels for our current understanding of the Cpx envelope stress response. The Cpx envelope stress response is regulated by a typical two-component regulatory system. In addition to functioning as an activator and a repressor, a new role for CpxR~P in transcription has recently been put forth, that of potentiator. Researchers have shown by microarray analysis of biofilm and planktonic populations of cells that the Cpx-regulated genes and were highly up-regulated in biofilms and that and mutants formed biofilms with reduced mass and substrate coverage. It has been shown that CpxR homologues in and are likely involved in transcription of the genes encoding the type IV secretion system and , respectively, both of which are necessary for virulence. Analysis of TraJ, TraY, and TraM protein half-lives in wild-type and Cpx-induced strains indicated that TraJ stability was specifically decreased when the Cpx response was activated. This study was the first to indicate that the Cpx response might influence the fates of intracellular proteins, in addition to those found in the envelope. The Cpx envelope stress response exhibits significant connectivity to other adaptive responses. Although it has become dogma that CpxA senses and is activated by misfolded envelope proteins, the mechanism(s) involved remain elusive.

Citation: Raivio T. 2007. The Cpx Envelope Stress Response, p 83-106. In Ehrmann M (ed), The Periplasm. ASM Press, Washington, DC. doi: 10.1128/9781555815806.ch5

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Gene Expression and Regulation
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Two-Component Signal Transduction Systems
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Transcription Start Site
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Type IV Secretion Systems
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Figures

Image of FIGURE 1
FIGURE 1

Independent genetic selections identified the Cpx locus. (Left) Silverman and colleagues selected conjugal F plasmid donors (right rectangle) that were resistant to the Qβ phage (hexagon), which adsorbs to the F pilus (thin grey line connecting donor and recipient cells). These mutants were defective in conjugal DNA transfer to F-recipient cells (left rectangle) and mapped to the locus. (Right) Silhavy and colleagues selected for mutants resistant to the expression of the toxic, misfolded, mislocalized proteins LamBA23D (rectangle joined to squiggly line) or a tribrid fusion protein LamB-LacZ-PhoA (squiggly line). LamBA23D contains a signal-sequence mutation that prevents cleavage of the signal sequence by leader peptidase (oval) and causes slowed processing, altered localization, and sensitivity to the inducer maltose (Mal) and SDS (SDS). LamB-LacZ-PhoA leads to the production of disulfide-bonded aggregates of β-galactosidase in the periplasm (squiggly line), which is manifest as sensitivity to the inducer maltose (Mal). SDS or Mal mutants mapped to the locus. OM, outer membrane; PP, periplasm; IM, inner membrane.

Citation: Raivio T. 2007. The Cpx Envelope Stress Response, p 83-106. In Ehrmann M (ed), The Periplasm. ASM Press, Washington, DC. doi: 10.1128/9781555815806.ch5
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Image of FIGURE 2
FIGURE 2

Cpx signal transduction is mediated by a two-component regulatory system. Envelope stresses are sensed by an inner membrane-localized sensor histidine kinase, CpxA. In the absence of envelope stress, CpxA functions as a CpxR~P (light shaded rectangle) phosphatase (dark shaded oval). In the presence of envelope stress, CpxA is thought to undergo a conformational change (dark shaded rectangle), which causes it to take on autokinase and CpxR (light shaded oval) kinase activities. Phos-phorylation of CpxR converts it to a transcription factor able to bind with increased affinity to the promoters of target genes. OM, outer membrane; PP, periplasm; IM, inner membrane; Pi, inorganic phosphate; H, histidine; D, aspartate; P, phosphate.

Citation: Raivio T. 2007. The Cpx Envelope Stress Response, p 83-106. In Ehrmann M (ed), The Periplasm. ASM Press, Washington, DC. doi: 10.1128/9781555815806.ch5
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Image of FIGURE 3
FIGURE 3

Cpx-inducing cues and -signaling proteins. All Cpx-inducing cues are sensed via the periplasmic sensing domain of CpxA (small shaded rectangle). Attachment to abiotic surfaces is signaled first through the outer membrane lipoprotein NlpE (shaded rectangle). Most other Cpx-inducing cues (boxed at bottom left) do not require NlpE for signaling. Some of these (pH, H/OH; P pilus subunit overexpression) lead to DegP-depen-dent degradation of the inhibitory signaling protein CpxP (light shaded oval in periplasm). Additional growth-related cues likely enter the signaling pathway downstream of CpxA but upstream of CpxR. PP, periplasm; IM, inner membrane; CYTO, cytoplasm; BFP, bundle-forming pilus.

Citation: Raivio T. 2007. The Cpx Envelope Stress Response, p 83-106. In Ehrmann M (ed), The Periplasm. ASM Press, Washington, DC. doi: 10.1128/9781555815806.ch5
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References

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1. Albin, R., and, P. M. Silverman. 1984. Identification of the Escherichia coli K-12 cpxA locus as a single gene: construction and analysis of biologically-active cpxA gene fusions. Mol. Gen. Genet. 197:272279.
2. Albin, R.,, R. Weber, and, P. M. Silverman. 1986. The Cpx proteins of Escherichia coli K12. Immuno-logic detection of the chromosomal cpxA gene product. J. Biol. Chem. 261:46984705.
3. Batchelor, E.,, D. Walthers,, L. J. Kenney, and, M. Goulian. 2005. The Escherichia coli CpxA-CpxR envelope stress response system regulates expression of the porins ompF and ompC. J. Bacteriol. 187:57235731.
4. Beck, N. A.,, E. S. Krukonis, and, V. J. DiRita. 2004. TcpH influences virulence gene expression in Vibrio cholerae by inhibiting degradation of the transcription activator TcpP. J. Bacteriol. 186:83098316.
5. Beloin, C.,, J. Valle,, P. Latour-Lambert,, P. Faure,, M. Kzreminski,, D. Balestrino,, J. A. Haa-gensen,, S. Molin,, G. Prensier,, B. Arbeille, and, J. M. Ghigo. 2004. Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression. Mol. Microbiol. 51:659674.
6. Buelow, D. R., and, T. L. Raivio. 2005. Cpx signal transduction is influenced by a conserved N-termi-nal domain in the novel inhibitor CpxP and the periplasmic protease DegP. J. Bacteriol. 187:66226630.
7. Carlson, J. H., and, T.J. Silhavy. 1993. Signal sequence processing is required for the assembly of LamB trimers in the outer membrane of Escherichia coli. J. Bacteriol. 175:33273334.
8. Cosma, C. L.,, P. N. Danese,, J. H. Carlson,, T. J. Sil-havy, and, W. B. Snyder. 1995. Activation of the Cpx two-component signal transduction pathway in Escherichia coli suppresses envelope associated stresses. Mol. Microbiol. 18:491505.
9. Danese, P. N.,, G. R. Oliver,, K. Barr,, G. D. Bowman,, P. D. Rick, and, T. J. Silhavy. 1998. Accumulation of the enterobacterial common antigen lipid II biosynthetic intermediate stimulates degP transcription in Escherichia coli. J. Bacteriol. 180: 58755884.
10. Danese, P. N., and, T. J. Silhavy. 1997. The σE and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli. Genes Dev. 11:11831193.
11. Danese, P. N., and, T. J. Silhavy. 1998. CpxP, a stress-combative member of the Cpx regulon. J. Bacteriol. 180:831839.
12. Danese, P. N.,, W. B. Snyder,, C. L. Cosma,, L. J. Davis, and, T. J. Silhavy. 1995. The Cpx two-component signal transduction pathway of Es-cherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 9:387398.
13. Dartigalongue, C.,, D. Missiakas, and, S. Raina. 2001. Characterization of the Escherichia coli sigma E regulon. J. Biol. Chem. 276:2086620875.
14. De Wulf, P.,, O. Kwon, and, E. C. C. Lin. 1999. The CpxRA signal transduction system of Escherichia coli: growth-related autoactivation and control of unanticipated target operons.J. Bacteriol. 181:65526778.
15. De Wulf, P.,, A. M. McGuire,, X. Liu, and, E. C. Lin. 2002. Genome-wide profiling of promoter recognition by the two-component response regulator CpxR-P in Escherichia coli. J. Biol. Chem. 277:2665226661.
16. DiGiuseppe, P. A., and, T. J. Silhavy. 2003. Signal detection and target gene induction by the CpxRA two-component system. J. Bacteriol. 185:24322440.
17. Dong, J. S.,, S. Iuchi,, S. Kwan,, Z. Lu, and, E. C. C. Lin. 1993. 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 136:227230.
18. Dorel, C.,, O. Vidal,, C. Prigent-Combaret,, I. Val-let, and, P. Lejeune. 1999. Involvement of the Cpx signal transduction pathway of E. coli in biofilm formation. FEMS Microbiol. Lett. 178:169175.
19. Erickson, J. W., and, C. A. Gross. 1989. Identification of the σE subunit of Escherichia coli RNA polymerase: a second alternate c factor involved in high-temperature gene expression. Genes Dev. 3: 14621471.
20. Gal-Mor, O., and, G. Segal. 2003. Identification of CpxR as a positive regulator of icm and dot virulence genes of Legionella pneumophila. J. Bacteriol. 185:49084919.
21. Grigorova, I. L.,, R. Chaba,, H. J. Zhong,, B. M. Alba,, V. Rhodius,, C. Herman, and, C. A. Gross. 2004. Fine-tuning of the Escherichia coli sigmaE envelope stress response relies on multiple mechanisms to inhibit signal-independent proteolysis of the transmembrane anti-sigma factor, RseA. Genes Dev. 18:26862697.
22. Gubbins, M.J.,, I. Lau,, W. R. Will,, J. M. Manchak,, T. L. Raivio, and, L. S. Frost. 2002. The positive regulator, TraJ, of the Escherichia coli F plasmid is unstable in a cpxA* background. J. Bacteriol. 184: 57815788.
23. Hernday, A. D.,, B. A. Braaten,, G. Broitman-Maduro,, P. Engelberts, and, D. A. Low. 2004. Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Mol. Cell 16:537547.
24. Heusipp, G.,, K. M. Nelson,, M. A. Schmidt, and, V. L. Miller. 2004. Regulation of htrA expression in Yersinia enterocolitica. FEMS Microbiol. Lett. 231: 227235.
25. Hirakawa, H.,, Y. Inazumi,, T. Masaki,, T. Hirata, and, A. Yamaguchi. 2005. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol. Microbiol. 55:11131126.
26. Hirakawa, H.,, K. Nishino,, T. Hirata, and, A. Yamaguchi. 2003. Comprehensive studies of drug resistance mediated by overexpression of response regulators of two-component signal transduction systems in Escherichia coli. J. Bacteriol. 185:18511856.
27. Humphreys, S.,, G. Rowley,, A. Stevenson,, M. F. Anjum,, M. J. Woodward,, S. Gilbert,, J. Kor-manec, and, M. Roberts. 2004. Role of the two-component regulator CpxAR in the virulence of Salmonella enterica serotype Typhimurium. Infect. Im-mun. 72 :46544661.
28. Hung, D. L.,, T. L. Raivio,, C. H. Jones,, T. J. Silhavy, and, S. J. Hultgren. 2001. Cpx signaling pathway monitors biogenesis and affects assembly and expression of P pili. EMBO J. 20:15081518.
29. Hunke, S., and, J. M. Betton. 2003. Temperature effect on inclusion body formation and stress response in the periplasm of Escherichia coli. Mol. Microbiol. 50:15791589.
30. Isaac, D. D.,, J. S. Pinkner,, S. J. Hultgren, and, T. J. Silhavy. 2005. The extracytoplasmic adaptor protein CpxP is degraded with substrate by DegP. Proc. Natl. Acad. Sci. USA 102:1777517779.
31. Jacob-Dubuisson, F.,, J. Pinkner,, X. Xu,, R. Striker,, A. Padmanhaban, and, S. J. Hultgren. 1994. PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of DsbA. Proc. Natl. Acad. Sci. USA 91:1155211556.
32. Jones, C. H.,, P. N. Danese,, J. S. Pinkner,, T. J. Sil-havy, and, S. J. Hultgren. 1997. The chaperone-assisted membrane release and folding pathway is sensed by two signal transduction systems. EMBO J. 21:63946406.
33. Jubelin, G.,, A. Vianney,, C. Beloin,, J. M. Ghigo,, J. C. Lazzaroni,, P. Lejeune, and, C. Dorel. 2005. CpxR/OmpR interplay regulates curli gene expression in response to osmolarity in Escherichia coli. J. Bacteriol. 187:20382049.
34. Lee, Y. M.,, P. A. DiGiuseppe,, T. J. Silhavy, and, S. J. Hultgren. 2004. P pilus assembly motif necessary for activation of the CpxRA pathway by PapE in Escherichia coli. J. Bacteriol. 186:43264337.
35. Lipinska, B.,, S. Sharma, and, C. Georgopoulos. 1988. Sequence analysis and regulation of the htrA gene of Escherichia coli:a σ32-independent mechanism of heat-inducible transcription. Nucleic Acids Res. 16:1005310067.
36. Martinez-Hackert, E., and, A. M. Stock. 1997. The DNA-binding domain of OmpR: crystal structures of a winged helix transcription factor. Structure 5:109124.
37. Matson, J. S., and, V. J. DiRita. 2005. Degradation of the membrane-localized virulence activator TcpP by the YaeL protease in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 102:1640316408.
38. McEwen, J.,, L. Sambucetti, and, P. M. Silverman. 1983. Synthesis of outer membrane proteins in cpxA cpxB mutants of Escherichia coli K-12. J. Bacte-riol. 154:375382.
39. McEwen, J., and, P. M. Silverman. 1980a. Chromosomal mutations of Escherichia coli that alter expression of conjugative plasmid functions. Proc. Natl. Acad. Sci. USA 77:513517.
40. McEwen, J., and, P. M. Silverman. 1980b. Genetic analysis of Escherichia coli K-12 chromosomal mutants defective in expression of F-plasmid functions: identification of genes cpxA and cpxB. J. Bacteriol. 144:6067.
41. McEwen, J., and, P. M. Silverman. 1980c. Mutations in genes cpxA and cpxB ofEscherichia coli K-12 cause a defect in isoleucine and valine syntheses. J. Bacteriol. 144:6873.
42. McEwen, J., and, P. M. Silverman. 1982. Mutations in genes cpxA and cpxB alter the protein composition of Escherichia coli inner and outer membranes. J. Bacteriol. 151:15531559.
43. Mileykovskaya, E., and, W. Dowhan. 1997. The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine .J. Bacteriol. 179:10291034.
44. Mitobe, J.,, E. Arakawa, and, H. Watanabe. 2005. A sensor of the two-component system CpxA affects expression of the type III secretion system through posttranscriptional processing of InvE.J. Bacteriol. 187:107113.
45. Miyadai, H.,, K. Tanaka-Masuda,, S. Matsuyama, and, H. Tokuda. 2004. Effects of lipoprotein overproduction on the induction of DegP (HtrA) involved in quality control in the Escherichia coli periplasm. J. Biol. Chem. 279:3980739813.
46. Nakayama, S.,, A. Kushiro,, T. Asahara,, R. Tanaka,, L. Hu,, D. J. Kopecko, and, H. Watanabe. 2003. Activation of hilA expression at low pH requires the signal sensor CpxA, but not the cognate response regulator CpxR, in Salmonella enterica serovar Typhimurium. Microbiology 149:28092817.
47. Nakayama, S.-I., and, H. Watanabe. 1995. Involvement of cpxA, a sensor of a two-component regulatory system, in the pH-dependent regulation of expression of Shigella sonnei virF gene.J. Bacteriol. 177:50625069.
48. Nakayama, S.-I., and, H. Watanabe. 1998. Identification of cpxR as a positive regulator essential for expression of the Shigella sonnei virF gene .J. Bacte-riol. 180:35223528.
49. Nevesinjac, A. Z., and, T. L. Raivio. 2005. The Cpx envelope stress response affects expression of the type IV bundle-forming pili of enteropathogenic Escherichia coli. J. Bacteriol. 187:672686.
50. Ogasawara, H.,, J. Teramoto,, K. Hirao,, K. Ya-mamoto,, A. Ishihama, and, R. Utsumi. 2004. Negative regulation of DNA repair gene (ung) expression by the CpxR/CpxA two-component system in Escherichia coli K-12 and induction of mutations by increased expression of CpxR.J. Bacteriol. 186:83178325.
51. Otto, K., and, T. J. Silhavy. 2002. Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling pathway. Proc. Natl. Acad. Sci. USA 99: 22872292.
52. Pogliano, J. A.,, S. Lynch,, D. Belin,, E. C. C. Lin, and, J. Beckwith. 1997. Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system.Genes Dev. 11:11691182.
53. Pratt, L. A., and, T. J. Silhavy. 1994. OmpR mutants specifically defective for transcriptional activation. J. Mol. Biol. 243:579594.
54. Prigent-Combaret, C.,, E. Brombacher,, O. Vidal,, A. Ambert,, P. Lejeune,, P. Landini, and, C. Dorel. 2001. Complex regulatory network controls initial adhesion and biofilm formation in Escherichia coli via regulation of the csgD gene. J. Bacteriol. 183:72137223.
55. Raffa, R. G., and, T. L. Raivio. 2002. A third envelope stress signal transduction pathway in Escherichia coli. Mol. Microbiol. 45:15991611.
56. Raina, S.,, D. Missiakas, and, C. Georgopoulos. 1995. The rpoE gene encoding the σE24) heat shock sigma factor of Escherichia coli. EMBO J. 14:10431055.
57. Rainwater, S., and, P. M. Silverman. 1990. The Cpx proteins of Escherichia coli K-12: evidence that cpxA, ecfB, ssd, and eup mutations all identify the same gene. J. Bacteriol. 172:24562461.
58. Raivio, T. L.,, M. W. Laird,, J. C. Joly, and, T. J. Sil-havy. (2000). Tethering of CpxP to the inner membrane prevents spheroplast induction of the Cpx envelope stress response .Mol. Microbiol. 37:11861197.
59. Raivio, T. L.,, D. L. Popkin, and, T. J. Silhavy. 1999. The Cpx envelope stress response is controlled by amplification and feedback inhibition. J. Bacteriol. 181:52635272.
60. Raivio, T. L., and, T. J. Silhavy. 1997. Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J. Bacteriol. 179:77247733.
61. Raivio, T. L., and, T. J. Silhavy. 1999. The σE and Cpx regulatory pathways: overlapping but distinct envelope stress responses. Curr. Opin. Microbiol. 2:159165.
62. Raivio, T. L., and, T. J. Silhavy. 2001. Periplasmic stress and ECF sigma factors. Annu. Rev. Microbiol. 55:591524.
63. Rouviere, P. E.,, A. De Las Penas,, J. Mecsas,, C. Z. Lu,, K. E. Rudd, and, C. A. Gross. 1995. rpoE, the gene encoding the second heat-shock sigma factor, σE, in Escherichia coli. EMBO J. 14:10321042.
64. Sauer, F. G.,, K. Futterer,, J. S. Pinkner,, K. W. Dodson,, S. J. Hultgren, and, G. Waksman. 1999. Structural basis of chaperone function and pilus biogenesis. Science 285:10581061.
65. Shimohata, N.,, S. Chiba,, N. Saikawa,, K. Ito, and, Y. Akiyama. 2002. The Cpx stress response system of Escherichia coli senses plasma membrane proteins and controls HtpX, a membrane protease with a cytosolic active site. Genes Cells 7:653662.
66. Silverman, P. M.,, L. Tran,, R. Harris, and, H. M. Gaudin. 1993. Accumulation of the F plasmid TraJ protein in cpx mutants of Escherichia coli. J. Bacteriol. 175:921925.
67. Snyder, W. B.,, L. J. B. Davis,, P. N. Danese,, C. L. Cosma, and, T. J. Silhavy. 1995. Overproduction of NlpE, a new outer membrane lipoprotein, suppresses the toxicity of periplasmic LacZ by activation of the Cpx signal transduction pathway. J. Bacteriol. 177:42164223.
68. Snyder, W. B., and, T. J. Silhavy. 1995. β-galactosi-dase is inactivated by intermolecular disulfide bonds and is toxic when secreted to the periplasm of Es-cherichia coli.J. Bacteriol. 177:953963.
69. Sutton, A.,, T. Newman,, J. McEwen,, P. M. Silverman, and, M. Freundlich. 1982. Mutations in genes cpxA and cpxB of Escherichia coli K-12 cause a defect in acetohydroxyacid synthase I function in vivo. J. Bacteriol. 151:976982.
70. Thanassi, D. G., and, S.J. Hultgren. 2000. Assem-bly of complex organelles:pilus biogenesis in gram-negative bacteria as a model system. Methods 20: 111126.
71. Weber, R. F., and, P. J. Silverman. 1988. The Cpx proteins of Escherichia coli K-12: structure of the CpxA polypeptide as an inner membrane component. J. Mol. Biol. 203:467476.
72. Wolfgang, M.,, J. P. van Putten,, S. F. Hayes,, D. Dorward, and, M. Koomey. 2000. Components and dynamics of fiber formation define a ubiquitous biogenesis pathway for bacterial pili. EMBO J. 19:64086418.
73. Zhang, H. Z., and, M. S. Donnenberg. 1996. DsbA is required for stability of the type IV pilin of en-teropathogenic Escherichia coli. Mol. Microbiol. 21: 787797.

Tables

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TABLE 1

The Cpx regulon

Citation: Raivio T. 2007. The Cpx Envelope Stress Response, p 83-106. In Ehrmann M (ed), The Periplasm. ASM Press, Washington, DC. doi: 10.1128/9781555815806.ch5

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