Home LiteratureArticle Details
PMID: 11285215 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cpx signaling pathway monitors biogenesis and affects assembly and expression of P pili.

The EMBO journal ·Vol. 20 ·No. 7 ·2001-04-02 ·Pages 1508-18

Hung DL, Raivio TL, Jones CH, Silhavy TJ, Hultgren SJ

Abstract

P pili are important virulence factors in uropathogenic Escherichia coli. The Cpx two-component signal transduction system controls a stress response and is activated by misfolded proteins in the periplasm. We have discovered new functions for the Cpx pathway, indicating that it may play a critical role in pathogenesis. P pili are assembled via the chaperone/usher pathway. Subunits that go 'OFF-pathway' during pilus biogenesis generate a signal. This signal is derived from the misfolding and aggregation of subunits that failed to come into contact with the chaperone in the periplasm. In response, Cpx not only controls the stress response, but also controls genes necessary for pilus biogenesis, and is involved in regulating the phase variation of pap expression and, potentially, the expression of a panoply of other virulence factors. This study demonstrates how the prototypic chaperone/usher pathway is intricately linked and dependent upon a signal transduction system.

MeSH Terms
Bacterial Proteins/genetics,metabolism,physiology Binding Sites Escherichia coli/genetics,metabolism,physiology Escherichia coli Proteins Fimbriae Proteins Fimbriae, Bacterial/physiology,ultrastructure Gene Expression Regulation, Bacterial Genes, Bacterial Heat-Shock Proteins/genetics,metabolism,physiology Membrane Proteins/genetics,metabolism Operon Periplasmic Proteins Protein Kinases/genetics,metabolism Serine Endopeptidases/genetics,metabolism,physiology Signal Transduction Transcription Factors/genetics
Chemicals
AtpA protein, E coli Bacterial Proteins CpxP protein, E coli CpxP protein, bacteria Escherichia coli Proteins Heat-Shock Proteins Membrane Proteins Periplasmic Proteins Transcription Factors atpD protein, E coli Fimbriae Proteins CpxR protein, Bacteria Protein Kinases CpxA protein, E coli CpxA protein, bacteria DegP protease Serine Endopeptidases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hung D L
Department of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
Raivio T L
Jones C H
Silhavy T J
Hultgren S J
References (73)
73 references, click to expand
  1. Accumulation of the enterobacterial common antigen lipid II biosynthetic intermediate stimulates degP transcription in Escherichia coli.
    J Bacteriol. 1998 Nov;180(22):5875-84 PMID: 9811644
  2. The chaperone/usher pathway: a major terminal branch of the general secretory pathway.
    Curr Opin Microbiol. 1998 Apr;1(2):223-31 PMID: 10066482
  3. Structural basis of chaperone self-capping in P pilus biogenesis.
    Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8178-83 PMID: 10393968
  4. Structural basis of chaperone function and pilus biogenesis.
    Science. 1999 Aug 13;285(5430):1058-61 PMID: 10446050
  5. X-ray structure of the FimC-FimH chaperone-adhesin complex from uropathogenic Escherichia coli.
    Science. 1999 Aug 13;285(5430):1061-6 PMID: 10446051
  6. The Cpx envelope stress response is controlled by amplification and feedback inhibition.
    J Bacteriol. 1999 Sep;181(17):5263-72 PMID: 10464196
  7. Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states.
    EMBO J. 1990 Dec;9(12):4045-54 PMID: 2147413
  8. Evidence for a methylation-blocking factor (mbf) locus involved in pap pilus expression and phase variation in Escherichia coli.
    J Bacteriol. 1991 Mar;173(5):1789-800 PMID: 1671857
  9. Saccharide orientation at the cell surface affects glycolipid receptor function.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9340-4 PMID: 1681550
  10. Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections.
    J Urol. 1996 Apr;155(4):1432-5 PMID: 8632605
  11. Molecular basis of two subfamilies of immunoglobulin-like chaperones.
    EMBO J. 1996 Aug 1;15(15):3792-805 PMID: 8670884
  12. Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses.
    Mol Microbiol. 1995 Nov;18(3):491-505 PMID: 8748033
  13. Two pathogenicity islands in uropathogenic Escherichia coli J96: cosmid cloning and sample sequencing.
    Infect Immun. 1996 Sep;64(9):3736-43 PMID: 8751923
  14. Epigenetic phase variation of the pap operon in Escherichia coli.
    Trends Microbiol. 1996 Jan;4(1):5-9 PMID: 8824788
  15. Transcriptional control mediated by the ArcA two-component response regulator protein of Escherichia coli: characterization of DNA binding at target promoters.
    J Bacteriol. 1996 Nov;178(21):6238-49 PMID: 8892825
  16. The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine.
    J Bacteriol. 1997 Feb;179(4):1029-34 PMID: 9023180
  17. Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system.
    Genes Dev. 1997 May 1;11(9):1169-82 PMID: 9159398
  18. The sigma(E) and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli.
    Genes Dev. 1997 May 1;11(9):1183-93 PMID: 9159399
  19. Pathogenicity island sequences of pyelonephritogenic Escherichia coli CFT073 are associated with virulent uropathogenic strains.
    Infect Immun. 1997 Jul;65(7):2812-20 PMID: 9199454
  20. Bacterial virulence in urinary tract infection.
    Infect Dis Clin North Am. 1997 Sep;11(3):513-29 PMID: 9378921
  21. Transduction of envelope stress in Escherichia coli by the Cpx two-component system.
    J Bacteriol. 1997 Dec;179(24):7724-33 PMID: 9401031
  22. The chaperone-assisted membrane release and folding pathway is sensed by two signal transduction systems.
    EMBO J. 1997 Nov 3;16(21):6394-406 PMID: 9351822
  23. CpxP, a stress-combative member of the Cpx regulon.
    J Bacteriol. 1998 Feb;180(4):831-9 PMID: 9473036
  24. Use of a two-color genetic screen to identify a domain of the global regulator Lrp that is specifically required for pap phase variation.
    J Bacteriol. 1998 Mar;180(5):1224-31 PMID: 9495762
  25. The PapC usher forms an oligomeric channel: implications for pilus biogenesis across the outer membrane.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3146-51 PMID: 9501230
  26. Ramifications of kinetic partitioning on usher-mediated pilus biogenesis.
    EMBO J. 1998 Apr 15;17(8):2177-85 PMID: 9545231
  27. In vivo phase variation of Escherichia coli type 1 fimbrial genes in women with urinary tract infection.
    Infect Immun. 1998 Jul;66(7):3303-10 PMID: 9632599
  28. Thermoregulation of Escherichia coli pap transcription: H-NS is a temperature-dependent DNA methylation blocking factor.
    Mol Microbiol. 1998 Jun;28(6):1121-37 PMID: 9680203
  29. Genomic analysis of a pathogenicity island in uropathogenic Escherichia coli CFT073: distribution of homologous sequences among isolates from patients with pyelonephritis, cystitis, and Catheter-associated bacteriuria and from fecal samples.
    Infect Immun. 1998 Sep;66(9):4411-7 PMID: 9712795
  30. P pili in uropathogenic E. coli are composite fibres with distinct fibrillar adhesive tips.
    Nature. 1992 Mar 19;356(6366):252-5 PMID: 1348107
  31. Conserved immunoglobulin-like features in a family of periplasmic pilus chaperones in bacteria.
    EMBO J. 1992 Apr;11(4):1617-22 PMID: 1348692
  32. Antirepression function in Escherichia coli for the cAMP-cAMP receptor protein transcriptional activator.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9880-4 PMID: 1384062
  33. Interactive surface in the PapD chaperone cleft is conserved in pilus chaperone superfamily and essential in subunit recognition and assembly.
    EMBO J. 1992 Dec;11(13):4747-56 PMID: 1361168
  34. Helical structure of P pili from Escherichia coli. Evidence from X-ray fiber diffraction and scanning transmission electron microscopy.
    J Mol Biol. 1992 Dec 5;228(3):735-42 PMID: 1361583
  35. Initiation of assembly and association of the structural elements of a bacterial pilus depend on two specialized tip proteins.
    EMBO J. 1993 Mar;12(3):837-47 PMID: 8096174
  36. Outer-membrane PapC molecular usher discriminately recognizes periplasmic chaperone-pilus subunit complexes.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3670-4 PMID: 8097321
  37. 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):227-30 PMID: 8294007
  38. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli.
    Cell. 1994 Feb 11;76(3):577-88 PMID: 7906204
  39. Regulation of Pap phase variation. Lrp is sufficient for the establishment of the phase off pap DNA methylation pattern and repression of pap transcription in vitro.
    J Biol Chem. 2000 Feb 4;275(5):3192-200 PMID: 10652304
  40. Nitric oxide in the lower urinary tract: physiological and pathological implications.
    BJU Int. 2000 Mar;85(5):567-78 PMID: 10735932
  41. PapD-like chaperones provide the missing information for folding of pilin proteins.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7709-14 PMID: 10859353
  42. Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8829-35 PMID: 10922042
  43. Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu.
    J Mol Biol. 1976 Jul 5;104(3):541-55 PMID: 781293
  44. Construction and expression of recombinant plasmids encoding type 1 or D-mannose-resistant pili from a urinary tract infection Escherichia coli isolate.
    Infect Immun. 1981 Sep;33(3):933-8 PMID: 6116675
  45. Genetics of digalactoside-binding adhesin from a uropathogenic Escherichia coli strain.
    Infect Immun. 1983 Sep;41(3):942-9 PMID: 6136465
  46. Nucleotide sequence of the papA gene encoding the Pap pilus subunit of human uropathogenic Escherichia coli.
    J Bacteriol. 1984 Jan;157(1):330-3 PMID: 6140260
  47. Genes of pyelonephritogenic E. coli required for digalactoside-specific agglutination of human cells.
    EMBO J. 1984 May;3(5):1167-73 PMID: 6145590
  48. Environmental temperature regulates transcription of a virulence pili operon in E. coli.
    EMBO J. 1984 Dec 1;3(12):2885-8 PMID: 6151898
  49. Specificity of binding of a strain of uropathogenic Escherichia coli to Gal alpha 1----4Gal-containing glycosphingolipids.
    J Biol Chem. 1985 Jul 15;260(14):8545-51 PMID: 3891756
  50. Role of type 1 pili and effects of phase variation on lower urinary tract infections produced by Escherichia coli.
    Infect Immun. 1985 Nov;50(2):370-7 PMID: 2865209
  51. Transcriptional activation of a pap pilus virulence operon from uropathogenic Escherichia coli.
    EMBO J. 1985 Dec 30;4(13B):3887-93 PMID: 2868893
  52. Improved single and multicopy lac-based cloning vectors for protein and operon fusions.
    Gene. 1987;53(1):85-96 PMID: 3596251
  53. An Escherichia coli mutation preventing degradation of abnormal periplasmic proteins.
    Proc Natl Acad Sci U S A. 1988 Mar;85(5):1576-80 PMID: 3278319
  54. 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):467-78 PMID: 3058985
  55. 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):2689-96 PMID: 2540154
  56. Phase-variation of pyelonephritis-associated pili in Escherichia coli: evidence for transcriptional regulation.
    EMBO J. 1989 Feb;8(2):613-20 PMID: 2656260
  57. In vivo expression and variation of Escherichia coli type 1 and P pili in the urine of adults with acute urinary tract infections.
    Infect Immun. 1989 Jun;57(6):1656-62 PMID: 2566580
  58. The PapG adhesin of uropathogenic Escherichia coli contains separate regions for receptor binding and for the incorporation into the pilus.
    Proc Natl Acad Sci U S A. 1989 Jun;86(12):4357-61 PMID: 2567514
  59. Autoregulation and multiple DNA interactions by a transcriptional regulatory protein in E. coli pili biogenesis.
    EMBO J. 1989 Apr;8(4):1271-7 PMID: 2568258
  60. Host-specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1-4Gal-containing isoreceptors.
    EMBO J. 1990 Jun;9(6):2001-10 PMID: 1693334
  61. Deletions of chromosomal regions coding for fimbriae and hemolysins occur in vitro and in vivo in various extraintestinal Escherichia coli isolates.
    Microb Pathog. 1990 Mar;8(3):213-25 PMID: 1974320
  62. Chaperone-assisted self-assembly of pili independent of cellular energy.
    J Biol Chem. 1994 Apr 29;269(17):12447-55 PMID: 7909802
  63. PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of DsbA.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11552-6 PMID: 7972100
  64. The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract.
    Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11889-93 PMID: 7991552
  65. Structural polymorphism of bacterial adhesion pili.
    Nature. 1995 Jan 12;373(6510):164-7 PMID: 7816100
  66. 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):387-98 PMID: 7883164
  67. Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and alpha-hemolysin form the pathogenicity island II of the uropathogenic Escherichia coli strain J96.
    FEMS Microbiol Lett. 1995 Feb 15;126(2):189-95 PMID: 7705611
  68. 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):4216-23 PMID: 7635808
  69. 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. 1995 Sep;177(17):5062-9 PMID: 7665485
  70. Specific binding of PapI to Lrp-pap DNA complexes.
    J Bacteriol. 1995 Nov;177(22):6449-55 PMID: 7592419
  71. Leucine-responsive regulatory protein plays dual roles as both an activator and a repressor of the Escherichia coli pap fimbrial operon.
    Mol Microbiol. 1995 Jul;17(2):303-12 PMID: 7494479
  72. Differential binding of Lrp to two sets of pap DNA binding sites mediated by Pap I regulates Pap phase variation in Escherichia coli.
    EMBO J. 1995 Dec 1;14(23):5785-97 PMID: 8846772
  73. Periplasmic chaperone recognition motif of subunits mediates quaternary interactions in the pilus.
    EMBO J. 1998 Nov 2;17(21):6155-67 PMID: 9799225
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2001-04-02
Pages
1508-18
Language
English
Region
England
NLM ID
8208664
PMCID
PMC145513
Subset
IM
Grants
NIDDK NIH HHS · R01DK51406 · United States
NIAID NIH HHS · AI07172-19 · United States
NIGMS NIH HHS · R01 GM034821 · United States
NIGMS NIH HHS · GM34821 · United States
NIDDK NIH HHS · R01 DK051406 · United States
NIAID NIH HHS · T32 AI007172 · United States
NIGMS NIH HHS · R37 GM034821 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com