Chapter 19 : Protein Export

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Protein Export, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818005/9781555812133_Chap19-1.gif /docserver/preview/fulltext/10.1128/9781555818005/9781555812133_Chap19-2.gif


This chapter describes what is known about protein export in from the perspective of the general mechanisms for protein export in gram-negative bacteria. Autotransporters constitute one terminal branch of the general secretory pathway (GSP), frequently employed to export virulence factors. A new Sec-independent system for translocation of proteins across the inner membrane (IM) has recently been identified, and orthologs of the essential genes of this system have been found in the genome. Sec-dependent translocation across the IM requires the substrate protein to be unfolded. Most ATP-binding cassette (ABC) transporters are, however, not involved in protein export, but in the efflux and influx of a diverse group of substrates. To date, none of the potential ABC transporters in has been proposed to be involved in protein export. Motility is mediated by the sheathed flagella in and is necessary for colonization in animal models. In the context of the chapter the flagellar export apparatus potentially is interesting owing to its similarity to type III export systems. Recently, in a different system, it has been demonstrated that the flagellar transport apparatus of also functions as a protein export system for a pathogenesis-related phospholipase, placing the flagellar export/assembly system under a new light. The proteins discussed in a section, urease, heat shock proteins, and superoxide dismutase, are found only in the cytoplasm of most bacterial species.

Citation: Ilver D, Rappoulli R, Telford J. 2001. Protein Export, p 219-226. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch19
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Akopyants, N. S.,, S. W. Clifton,, D. Kersulyte,, J. E. Crabtree,, B. E. Youree,, C. A. Reece,, N. O. Bukanov,, E. S. Drazek,, B. A. Roe,, and D. E. Berg. 1998. Analyses of the cag pathogenicity island of Helicobacter pylori. Mol. Microbiol. 28:3753.
2. Alm, R. A.,, L. S. Ling,, D. T. Molr,, B. L. King,, E. D. Brown,, P. C. Doig,, D. R. Smith,, B. Noonan,, B. C. Guild,, B. L. deJonge,, G. Carmel,, P. J. Tummino,, A. Caruso,, M. Uria-Nickelsen,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang,, D. E. Taylor,, G. F. Vovis,, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176180. (Erratum, 397:719.)
3. Asahi, M.,, T. Azuma,, S. Ito,, Y. Ito,, H. Suto,, Y. Nagai,, M. Tsubokawa,, Y. Tohyama,, S. Maeda,, M. Omata,, T. Suzuki,, and C. Sasakawa. 2000. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J. Exp. Med. 191:593602.
4. Berry, A. M.,, J. C. Paton,, and D. Hansman. 1992. Effect of insertional inactivation of the genes encoding pneumolysin and autolysin on the virulence of Streptococcus pneumoniae type 3. Microb. Pathog. 12:8793.
5. Beveridge, T. J. 1999. Structures of gram-negative cell walls and their derived membrane vesicles. J. Bacteriol. 181: 47254733.
6. Binet, R.,, S. Letoffe,, J. M. Ghigo,, P. Delepelaire,, and C. Wandersman. 1997. Protein secretion by gram-negative bacterial ABC exporters—a review. Gene 192:711.
7. Blaser, M. J.,, and J. Parsonnet. 1994. Parasitism by the "slow" bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J. Clin. Invest. 94:48.
9. Censini, S.,, C. Lange,, Z. Xiang,, J. E. Crabtree,, P. Ghiara,, M. Borodovsky,, R. Rappuoli,, and A. Covacci. 1996. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc. Natl. Acad. Sci. USA 93:1464814653.
10. Christie, P. J.,, and J. P. Vogel. 2000. Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends Microbiol. 8:354360.
11. Covacci, A.,, S. Censini,, M. Bugnoli,, R. Petracca,, D. Burroni,, G. Macchia,, A. Massone,, E. Papini,, Z. Xiang,, N. Figura,, and R. Rappuoli. 1993. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc. Natl. Acad. Sci. USA 90:57915795.
12. Cover, T. L.,, M. K. Tummuru,, P. Cao,, S. A. Thompson,, and M. J. Blaser. 1994. Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J. Biol. Chem. 269:1056610573.
13. Dalbey, R. E.,, and C. Robinson. 1999. Protein translocation into and across the bacterial plasma membrane and the plant thylakoid membrane. Trends Biochem. Sci. 24:1722.
14. Dunn, B. E.,, N. B. Vakil,, B. G. Schneider,, M. M. Miller,, J. B. Zitzer,, T. Peutz,, and S. H. Phadnis. 1997. Localization of Helicobacter pylori urease and heat shock protein in human gastric biopsies. Infect. Immun. 65:11811188.
15. Eaton, K. A.,, C. L. Brooks,, D. R. Morgan,, and S. Krakowka. 1991. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 59:24702475.
16. Eaton, K. A.,, and S. Krakowka. 1994. Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori. Infect. Immun. 62:36043607.
17. Eaton, K. A.,, S. Suerbaum,, C. Josenhans,, and S. Krakowka. 1996. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun. 64: 24452448.
18. Economou, A. 1999. Following the leader: bacterial protein export through the Sec pathway. Trends Microbiol. 7: 315320.
19. Eschweiler, B.,, B. Bohrmann,, B. Gerstenecker,, E. Schiltz,, and M. Kist. 1993. In situ localization of the 60 k protein of Helicobacter pylori, which belongs to the family of heat shock proteins, by immuno-electron microscopy. Zentralbl. Bakteriol. 280:7385.
20. Fiocca, R.,, V. Necchi,, P. Sommi,, V. Ricci,, J. Telford,, T. L. Cover,, and E. Solcia. 1999. Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium. J. Pathol. 188:220226.
21. Fisher, W.,, and R. Haas. Personal communication.
22. Geis, G.,, H. Leying,, S. Suerbaum,, U. Mai,, and W. Opferkuch. 1989. Ultrastructure and chemical analysis of Campylobacter pylori flagella. J. Clin. Microbiol. 27:436441.
23. Hawtin, P. R.,, A. R. Stacey,, and D. G. Newell. 1990. Investigation of the structure and localization of the urease of Helicobacter pylori using monoclonal antibodies. J. Gen. Microbiol. 136(Pt 10):19952000.
24. Horstman, A. L.,, and M. J. Kuehn. 2000. Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles. J. Biol. Chem. 275:1248912496.
25. Hueck, C. J. 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62:379433.
26. Jenks, P. J.,, S. Foynes,, S. J. Ward,, C. Constantinidou,, C. W. Penn,, and B. W. Wren. 1997. A flagellar-specific ATPase (Flil) is necessary for flagellar export in Helicobacter pylori. FEMS Microbiol. Lett. 152:205211.
27. Jonsson, A. B.,, G. Nyberg,, and S. Normark. 1991. Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J. 10:477488.
28. Kadurugamuwa, J. L.,, and T. J. Beveridge. 1996. Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: conceptually new antibiotics. J. Bacteriol. 178:27672774.
29. Kadurugamuwa, J. L.,, and T. J. Beveridge. 1998. Delivery of the non-membrane-permeative antibiotic gentamicin into mammalian cells by using Shigella flexneri membrane vesicles. Antimicrob. Agents Chemother. 42:14761483.
30. Kadurugamuwa, J. L.,, and T. J. Beveridge. 1995. Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. J. Bacteriol. 177:39984008.
31. Keenan, J.,, T. Day,, S. Neal,, B. Cook,, G. Perez-Perez,, R. Allardyce,, and P. Bagshaw. 2000. A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection. FEMS Microbiol. Lett. 182:259264.
32. Klauser, T.,, J. Pohlner,, and T. F. Meyer. 1990. Extracellular transport of cholera toxin B subunit using Neisseria IgA protease beta-domain: conformation-dependent outer membrane translocation. EMBO J. 9:19911999.
33. Krishnamurthy, P.,, M. Parlow,, J. B. Zitzer,, N. B. Vakil,, H. L. Mobley,, M. Levy,, S. H. Phadnis,, and B. E. Dunn. 1998. Helicobacter pylori containing only cytoplasmic urease is susceptible to acid. Infect. Immun. 66:50605066.
34. Kubori, T.,, Y. Matsushima,, D. Nakamura,, J. Uralil,, M. Lara-Tejero,, A. Sukhan,, J. E. Galan,, and S. I. Aizawa. 1998. Supra-molecular structure of the Salmonella typhimurium type III protein secretion system. Science 280:602605.
35. Leying, H.,, S. Suerbaum,, G. Geis,, and R. Haas. 1992. Cloning and genetic characterization of a Helicobacter pylori flagellin gene. Mol. Microbiol. 6:28632874.
36. Maurer, J.,, J. Jose,, and T. F. Meyer. 1999. Characterization of the essential transport function of the AIDA-I autotransporter and evidence supporting structural predictions. J. Bacteriol. 181:70147020.
37. Nguyen, L.,, I. T. Paulsen,, J. Tchieu,, C. J. Hueck,, and M. H. Saier, Jr. 2000. Phylogenetic analyses of the constituents of type III protein secretion systems. J. Mol. Microbiol Biotechnol. 2:125144.
38. O'Toole, P. W.,, M. Kostrzynska,, and T. J. Trust. 1994. Non-motile mutants of Helicobacter pylori and Helicobacter mustelae defective in flagellar hook production. Mol. Microbiol. 14:691703.
39. Odenbreit, S.,, J. Puis,, B. Sedlmaier,, E. Gerland,, W. Fischer,, and R. Haas. 2000. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287: 14971500.
40. Paton, J. C.,, P. W. Andrew,, G. J. Boulnois,, and T. J. Mitchell. 1993. Molecular analysis of the pathogenicity of Streptococcus pneumoniae: the role of pneumococcal proteins. Annu. Rev. Microbiol. 47:89115.
41. Paulsen, I. T.,, L. Nguyen,, M. K. Sliwinski,, R. Rabus,, and M. H. Saier, Jr. 2000. Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes. J. Mol. Biol. 301:75100.
42. Phadnis, S. H.,, D. liver,, L. Janzon,, S. Normark,, and T. U. Westblom. 1994. Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect. Immun. 62:15571565.
43. Phadnis, S. H.,, M. H. Parlow,, M. Levy,, D. liver,, C. M. Caulkins,, J. B. Connors,, and B. E. Dunn. 1996. Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis. Infect. Immun. 64:905912.
44. Pohlner, J.,, R. Halter,, K. Beyreuther,, and T. F. Meyer. 1987. Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. Nature 325:458462.
45. Porwollik, S.,, B. Noonan,, and P. W. O'Toole. 1999. Molecular characterization of a flagellar export locus of Helicobacter pylori. Infect. Immun. 67:20602070.
46. Russel, M. 1998. Macromolecular assembly and secretion across the bacterial cell envelope: type II protein secretion systems. J. Mol. Biol. 279:485499.
47. Santini, C. L.,, B. Ize,, A. Chanal,, M. Muller,, G. Giordano,, and L. F. Wu. 1998. A novel sec-independent periplasmic protein translocation pathway in Escherichia coli. EMBO J. 17: 101112.
48. Sargent, F.,, N. R. Stanley,, B. C. Berks,, and T. Palmer. 1999. Sec-independent protein translocation in Escherichia coli. A distinct and pivotal role for the TatB protein. J. Biol. Chem. 274:3607336082.
49. Schmitt, W.,, and R. Haas. 1994. Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. Mol. Microbiol. 12: 307319.
50. Schraw, W.,, M. S. McClain,, and T. L. Cover. 1999. Kinetics and mechanisms of extracellular protein release by Helicobacter pylori. Infect. Immun. 67:52475252.
51. Segal, E. D.,, J. Cha,, J. Lo,, S. Falkow,, and L. S. Tompkins. 1999. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. USA 96:1455914564.
52. Segal, E. D.,, C. Lange,, A. Covacci,, L. S. Tompkins,, and S. Falkow. 1997. Induction of host signal transduction pathways by Helicobacter pylori. Proc. Natl. Acad. Sci. USA 94: 75957599.
53. Seifert, H. S.,, R. S. Ajioka,, C. Marchal,, P. F. Sparling,, and M. So. 1988. DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae. Nature 336:392395.
54. Settles, A. M.,, and R. Martienssen. 1998. Old and new pathways of protein export in chloroplasts and bacteria. Trends Cell. Biol. 8:494501.
55. Sommi, P.,, V. Ricci,, R. Fiocca,, V. Necchi,, M. Romano,, J. L. Telford,, E. Solcia,, and U. Ventura. 1998. Persistence of Helicobacter pylori VacA toxin and vacuolating potential in cultured gastric epithelial cells. Am. J. Physiol. 275(4 Pt 1):G681G688.
56. Spiegelhalder, C.,, B. Gerstenecker,, A. Kersten,, E. Schiltz,, and M. Kist. 1993. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect. Immun. 61:53155325.
57. Stein, M.,, R. Rappuoli,, and A. Covacci. 2000. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc. Natl. Acad. Sci. USA 97: 12631268.
58. Suzuki, T.,, M. C. Lett,, and C. Sasakawa. 1995. Extracellular transport of VirG protein in Shigella. J. Biol. Chem. 270: 3087430880.
59. Telford, J. L.,, P. Ghiara,, M. Dell'Orco,, M. Comanducci,, D. Burroni,, M. Bugnoli,, M. F. Tecce,, S. Censini,, A. Covacci,, Z. Xiang,, E. Papini,, C. Montecucco,, L. Parente,, and R. Rappuoli. 1994. Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J. Exp. Med. 179: 16531658.
60. Thanassi, D. G.,, E. T. Saulino,, and S.J. Hultgren. 1998. The chaperone/usher pathway: a major terminal branch of the general secretory pathway. Curr. Opin. Microbiol. 1:223231.
61. The Institute for Genomic Research, http://www.tigr.org/.
62. Tomb, J.-F.,, O. White,, A. R. Kerlavage,, R. A. Clayton,, G. G. Sutton,, R. D. Fleischmann,, K. A. Ketchum,, H. P. Klenk,, S. Gill,, B. A. Dougherty,, K. Nelson,, J. Quackenbush,, L. Zhou,, E. F. Kirkness,, S. Peterson,, B. Loftus,, D. Richardson,, R. Dodson,, H. G. Khalak,, A. Glodek,, K. McKenney,, L. M. Fitzgerald,, N. Lee,, M. D. Adams,, E. K. Hickey,, D. E. Berg,, J. D. Gocayne,, T. R. Utterback,, J. D. Peterson,, J. M. Kelley,, M. D. Cotton,, J. M. Weidman,, C. Fujii,, C. Bowman,, L. Watthey,, E. Wallin,, W. S. Hayes,, M. Borodovsky,, P. D. Karp,, H. O. Smith,, C. M. Fraser,, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539547. (Erratum, 389:412.)
63. Vanet, A.,, and A. Labigne. 1998. Evidence for specific secretion rather than autolysis in the release of some Helicobacter pylori proteins. Infect. Immun. 66:10231027.
64. Veiga, E.,, V. de Lorenzo,, and L. A. Fernandez. 1999. Probing secretion and translocation of a beta-autotransporter using a reporter single-chain Fv as a cognate passenger domain. Mol. Microbiol. 33:12321243.
65. Xiang, Z.,, S. Censini,, P. F. Bayeli,, J. L. Telford,, N. Figura,, R. Rappuoli,, and A. Covacci. 1995. Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect. Immun. 63:9498.
66. Young, G. M.,, D. H. Schmiel,, and V. L. Miller. 1999. A new pathway for the secretion of virulence factors by bacteria: the flagellar export apparatus functions as a protein-secretion system. Proc. Natl. Acad. Sci. USA 96:64566461.


Generic image for table
Table 1

Summary of protein export in

Citation: Ilver D, Rappoulli R, Telford J. 2001. Protein Export, p 219-226. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch19

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error