Chapter 15 : Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection

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

Preview this chapter:
Zoom in

Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap15-2.gif


Host responses elicited by type IV secretion systems (T4SS) activity are important factors in determining whether the infection will be resolved or whether bacteria will be able to cause a persistent infection. This chapter discusses recent findings on the functions of T4SS of , , , species, and species as well as new information gained from animal and cellular models of infection on how the secreted substrates alter the host’s response to infection. species are facultative intracellular pathogens found ubiquitously in freshwater environments, where they invade and replicate within amoebae and other protozoa. Importantly, NF- κB translocation is essential for the intracellular survival of , as the inhibition of this process resulted in the death of infected cells and prevented further bacterial replication when macrophages were infected at a low multiplicity of infection in a previous study. Studies of the global transcriptional response of gastric epithelial cells to infection have shed light on the contribution of the T4SS to chronic inflammation and gastric cancer. Although the Dot/Icm T4SS transfers DNA by conjugation in vitro, it is not known whether DNA can be translocated into host cells during infection. The popularity of employing T4SS for host-pathogen interaction may be due in part to the fact that these virulence factors can accommodate the secretion of distinct sets of effector proteins, thereby enabling each pathogen to adapt to a different specific niche.

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15

Key Concept Ranking

Mitogen-Activated Protein Kinase Pathway
Tumor Necrosis Factor alpha
Type IV Secretion Systems
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Assembly and function of the Dot/Icm T4SS. ARF, ADP-ribosylation factor; CP, bacterial cytoplasm; CM, cytoplasmic membrane; PP, periplasm; OM, outer membrane; LPS, lipopolysaccharide; PM, plasma membrane; P-L, phagosome-lysosome. The assembly of the T4SS complex is inferred in part based on work on the T4SS, which is reviewed in references and .

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Assembly and function of the Cag PAI T4SS. PGN, peptidoglycan; P, phosphorylation. Other abbreviations are as defined in the legend to Fig. 1 . The assembly of the T4SS complex is inferred in part based on work on the T4SS, which is reviewed in references and .

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Assembly and function of the VirB T4SS. Abbreviations are as defined in the legend to Fig. 2 . The assembly of the T4SS complex is inferred in part based on work on the T4SS, which is reviewed in references and .

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abu-Zant, A.,, S. Jones,, R. Asare,, J. Suttles,, C. Price,, J. Graham, and, Y. A. Kwaik. 2006. Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila. Cell. Microbiol. 9:246264.
2. 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.
3. Amer, A.,, L. Franchi,, T. D. Kanneganti,, M. Body-Malapel,, N. Ozoren,, G. Brady,, S. Meshinchi,, R. Jagirdar,, A. Gewirtz,, S. Akira, and, G. Nunez. 2006. Regulation of Legionella phagosome maturation and infection through flagellin and host IpaF. J. Biol. Chem. 281:3521735223.
4. Andersson, S. G.,, A. Zomorodipour,, J. O. Andersson,, T. Sicheritz-Ponten,, U. C. Alsmark,, R. M. Podowski,, A. K. Naslund,, A. S. Eriksson,, H. H. Winkler, and, C. G. Kurland. 1998. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396:133140.
5. Andrews, H. L.,, J. P. Vogel, and, R. R. Isberg. 1998. Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect. Immun. 66:950958.
6. 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.
7. Bach, S.,, A. Makristathis,, M. Rotter, and, A. M. Hirschl. 2002. Gene expression profiling in AGS cells stimulated with Helicobacter pylori isogenic strains (cagA positive or cagA negative). Infect. Immun. 70:988992.
8. Backert, S., and, T. F. Meyer. 2006. Type IV secretion systems and their effectors in bacterial pathogenesis. Curr. Opin. Microbiol. 9:207217.
9. Backert, S.,, E. Ziska,, V. Brinkmann,, U. Zimny-Arndt,, A. Fauconnier,, P. R. Jung-blut,, M. Naumann, and, T. F. Meyer. 2000. Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell. Microbiol. 2:155164.
10. Baron, C. 2005. From bioremediation to biowarfare: on the impact and mechanism of type IV secretion systems. FEMS Microbiol. Lett. 253:163170.
11. Batchelor, R. A.,, B. M. Pearson,, L. M. Friis,, P. Guerry, and, J. M. Wells. 2004. Nucleotide sequences and comparison of two large conjugative plasmids from different Campylobacter species. Microbiology 150:35073517.
12. Belcher, C. E.,, J. Drenkow,, B. Kehoe,, T. R. Gingeras,, N. McNamara,, H. Lemjabbar,, C. Basbaum, and, D. A. Relman. 2000. The transcriptional responses of respiratory epithelial cells to Bordetella pertussis reveal host defensive and pathogen counter-defensive strategies. Proc. Natl. Acad. Sci. USA 97:1384713852.
13. Berger, K. H.,, J. J. Merriam, and, R. R. Isberg. 1994. Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol. Microbiol. 14:809822.
14. Beswick, E. J.,, I. V. Pinchuk,, G. Suarez,, J. C. Sierra, and, V. E. Reyes. 2006. Helicobacter pylori CagA-dependent macrophage migration inhibitory factor produced by gastric epithelial cells binds to CD74 and stimulates procarcinogenic events. J. Immunol. 176:67946801.
15. Boldrick, J. C.,, A. A. Alizadeh,, M. Diehn,, S. Dudoit,, C. L. Liu,, C. E. Belcher,, D. Botstein,, L. M. Staudt,, P. O. Brown, and, D. A. Relman. 2002. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc. Natl. Acad. Sci. USA 99:972977.
16. Boschiroli, M. L.,, S. Ouahrani-Bettache,, V. Foulongne,, S. Michaux-Charachon,, G. Bourg,, A. Allardet-Servent,, C. Cazevieille,, J. P. Liautard,, M. Ramuz, and, D. O’Callaghan. 2002. The Brucella suis virB operon is induced intracellularly in macrophages. Proc. Natl. Acad. Sci. USA 99:15441549.
17. Brand, B. C.,, A. B. Sadosky, and, H. A. Shuman. 1994. The Legionella pneumophila icm locus: a set of genes required for intracellular multiplication in human macrophages. Mol. Microbiol. 14:797808.
18. Burns, D. L.,, E. L. Hewlett,, J. Moss, and, M. Vaughan. 1983. Pertussis toxin inhibits enkephalin stimulation of GTPase of NG108-15 cells. J. Biol. Chem. 258:14351438.
19. Celli, J.,, C. de Chastellier,, D. M. Fran chini,, J. Pizarro-Cerda,, E. Moreno, and, J. P. Gorvel. 2003. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J. Exp. Med. 198:545556.
20. Celli, J.,, S. P. Salcedo, and, J. P. Gorvel. 2005. Brucella coopts the small GTPase Sar1 for intracellular replication. Proc. Natl. Acad. Sci. USA 102:16731678.
21. 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.
22. Chen, J.,, K. S. de Felipe,, M. Clarke,, H. Lu,, O. R. Anderson,, G. Segal, and, H. A. Shuman. 2004. Legionella effectors that promote nonlytic release from protozoa. Science 303:13581361.
23. Chiou, C. C.,, C. C. Chan,, D. L. Sheu,, K. T. Chen,, Y. S. Li, and, E. C. Chan. 2001. Helicobacter pylori infection induced alteration of gene expression in human gastric cells. Gut 48:598604.
24. Christie, P. J.,, K. Atmakuri,, V. Krishna-moorthy,, S. Jakubowski, and, E. Cascales. 2005. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59:451485.
25. 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.
26. Coers, J.,, J. C. Kagan,, M. Matthews,, H. Nagai,, D. M. Zuckman, and, C. R. Roy. 2000. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Mol. Microbiol. 38:719736.
27. Comerci, D. J.,, M. J. Martinez-Lorenzo,, R. Sieira,, J. P. Gorvel, and, R. A. Ugalde. 2001. Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole. Cell. Microbiol. 3:159168.
28. Covacci, A., and, R. Rappuoli. 1993. Pertussis toxin export requires accessory genes located downstream from the pertussis toxin operon. Mol. Microbiol. 8:429434.
29. Cox, J. M.,, C. L. Clayton,, T. Tomita,, D. M. Wallace,, P. A. Robinson, and, J. E. Crabtree. 2001. cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes. Infect. Immun. 69:69706980.
30. de Felipe, K. S.,, S. Pampou,, O. S. Jovanovic,, C. D. Pericone,, S. F. Ye,, S. Kalachikov, and, H. A. Shuman. 2005. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187:77167726.
31. Dehio, C. 2001. Bartonella interactions with endothelial cells and erythrocytes. Trends Microbiol. 9:279285.
32. Dehio, C.,, M. Meyer,, J. Berger,, H. Schwarz, and, C. Lanz. 1997. Interaction of Bartonella henselae with endothelial cells results in bacterial aggregation on the cell surface and the subsequent engulfment and internalisation of the bacterial aggregate by a unique structure, the invasome. J. Cell Sci. 110:21412154.
33. Dehio, M.,, M. Quebatte,, S. Foser, and, U. Certa. 2005. The transcriptional response of human endothelial cells to infection with Bartonella henselae is dominated by genes controlling innate immune responses, cell cycle, and vascular remodelling. Thromb. Haemost. 94:347361.
34. Delrue, R. M.,, M. Martinez-Lorenzo,, P. Lestrate,, I. Danese,, V. Bielarz,, P. Mertens,, X. De Bolle,, A. Tibor,, J. P. Gorvel, and, J. J. Letesson. 2001. Identification of Brucella spp. genes involved in intracellular trafficking. Cell. Microbiol. 3:487497.
35. den Hartigh, A. B.,, Y. H. Sun,, D. Sondervan,, N. Heuvelmans,, M. O. Reinders,, T. A. Ficht, and, R. M. Tsolis. 2004. Differential requirements for VirB1 and VirB2 during Brucella abortus infection. Infect. Immun. 72:51435149.
36. Economou, A.,, P. J. Christie,, R. C. Fern-andez,, T. Palmer,, G. V. Plano, and, A. P. Pugsley. 2006. Secretion by numbers: protein traffic in prokaryotes. Mol. Microbiol. 62:308319.
37. Edelstein, P. H.,, M. A. Edelstein,, F. Higa, and, S. Falkow. 1999. Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model. Proc. Natl. Acad. Sci. USA 96:81908195.
38. Falush, D.,, C. Kraft,, N. S. Taylor,, P. Correa,, J. G. Fox,, M. Achtman, and, S. Suerbaum. 2001. Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age. Proc. Natl. Acad. Sci. USA 98:1505615061.
39. Farizo, K. M.,, T. G. Cafarella, and, D. L. Burns. 1996. Evidence for a ninth gene, ptlI, in the locus encoding the pertussis toxin secretion system of Bordetella pertussis and formation of a PtlI-PtlF complex. J. Biol. Chem. 271:3164331649.
40. Farizo, K. M.,, T. Huang, and, D. L. Burns. 2000. Importance of holotoxin assembly in Ptl-mediated secretion of pertussis toxin from Bordetella pertussis. Infect. Immun. 68:40494054.
41. Fields, B. S. 1996. The molecular ecology of legionellae. Trends Microbiol. 4:286290.
42. Foulongne, V.,, G. Bourg,, C. Cazevieille,, S. Michaux-Charachon, and, D. O’Callaghan. 2000. Identification of Brucella suis genes affecting intracellular survival in an in vitro human macrophage infection model by signature-tagged transposon mutagenesis. Infect. Immun. 68:12971303.
43. Frank, A. C.,, C. M. Alsmark,, M. Thollesson, and, S. G. Andersson. 2005. Functional divergence and horizontal transfer of type IV secretion systems. Mol. Biol. Evol. 22:13251336.
44. Fraser, D. W.,, T. R. Tsai,, W. Orenstein,, W. E. Parkin,, H. J. Beecham,, R. G. Sharrar,, J. Harris,, G. F. Mallison,, S. M. Martin,, J. E. McDade,, C. C. Shepard, and, P. S. Brachman. 1977. Legionnaires’ disease: description of an epidemic of pneumonia. N. Engl. J. Med. 297:11891197.
45. Galgani, M.,, I. Busiello,, S. Censini,, S. Zappacosta,, L. Racioppi, and, R. Zarrilli. 2004. Helicobacter pylori induces apoptosis of human monocytes but not monocyte-derived dendritic cells: role of the cag pathogenicity island. Infect. Immun. 72:44804485.
46. Galli, D. M.,, J. Chen,, K. F. Novak, and, D. J. Leblanc. 2001. Nucleotide sequence and analysis of conjugative plasmid pVT745. J. Bacteriol. 183:15851594.
47. Gao, L. Y., and, Y. A. Kwaik. 2000. The modulation of host cell apoptosis by intracellular bacterial pathogens. Trends Microbiol. 8:306313.
48. Goodwin, M. S., and, A. A. Weiss. 1990. Adenylate cyclase toxin is critical for colonization and pertussis toxin is critical for lethal infection by Bordetella pertussis in infant mice. Infect. Immun. 58:34453447.
49. Gross, A.,, A. Terraza,, S. Ouahrani-Bettache,, J. P. Liautard, and, J. Dornand. 2000. In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells. Infect. Immun. 68:342351.
50. Guillemin, K.,, N. R. Salama,, L. S. Tompkins, and, S. Falkow. 2002. Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA 99:1513615141.
51. Hamilton, H. L.,, N. M. Dominguez,, K. J. Schwartz,, K. T. Hackett, and, J. P. Dillard. 2005. Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system. Mol. Microbiol. 55:17041721.
52. Hatakeyama, M., and, H. Higashi. 2005. Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis. Cancer Sci. 96:835843.
53. He, Y.,, S. Reichow,, S. Ramamoorthy,, X. Ding,, R. Lathigra,, J. C. Craig,, B. W. Sobral,, G. G. Schurig,, N. Sriranganathan, and, S. M. Boyle. 2006. Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondrion-associated gene expression in mouse macrophages. Infect. Immun. 74:50355046.
54. Higashi, H.,, K. Yokoyama,, Y. Fujii,, S. Ren,, H. Yuasa,, I. Saadat,, N. Murata-Kamiya,, T. Azuma, and, M. Hatakeyama. 2005. EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. J. Biol. Chem. 280:2313023137.
55. Hofreuter, D.,, S. Odenbreit, and, R. Haas. 2001. Natural transformation competence in Helicobacter pylori is mediated by the basic components of a type IV secretion system. Mol. Microbiol. 41:379391.
56. Hofreuter, D.,, S. Odenbreit,, G. Henke, and, R. Haas. 1998. Natural competence for DNA transformation in Helicobacter pylori: identification and genetic characterization of the comB locus. Mol. Microbiol. 28:10271038.
57. Hong, P. C.,, R. M. Tsolis, and, T. A. Ficht. 2000. Identification of genes required for chronic persistence of Brucella abortus in mice. Infect. Immun. 68:41024107.
58. Huff, J. L.,, L. M. Hansen, and, J. V. Solnick. 2004. Gastric transcription profile of Helicobacter pylori infection in the rhesus macaque. Infect. Immun. 72:52165226.
59. Ishii, K. J.,, C. Coban,, H. Kato,, K. Takahashi,, Y. Torii,, F. Takeshita,, H. Ludwig,, G. Sutter,, K. Suzuki,, H. Hemmi,, S. Sato,, M. Yamamoto,, S. Uematsu,, T. Kawai,, O. Takeuchi, and, S. Akira. 2006. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat. Immunol. 7:4048.
60. Kahl-McDonagh, M. M.,, P. H. Elzer,, S. D. Hagius,, J. V. Walker,, Q. L. Perry,, C. M. Seabury,, A. B. den Hartigh,, R. M. Tsolis,, L. G. Adams,, D. S. Davis, and, T. A. Ficht. 2006. Evaluation of novel Brucella melitensis unmarked deletion mutants for safety and efficacy in the goat model of brucellosis. Vaccine 24:51695177.
61. Katada, T.,, M. Tamura, and, M. Ui. 1983. The A protomer of islet-activating protein, pertussis toxin, as an active peptide catalyzing ADPribosylation of a membrane protein. Arch. Biochem. Biophys. 224:290298.
62. Katada, T., and, M. Ui. 1982. Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc. Natl. Acad. Sci. USA 79:31293133.
63. Kerr, I. M., and, G. R. Stark. 1992. The anti-viral effects of the interferons and their inhibition. J. Interferon Res. 12:237240.
64. Kirby, J. E., and, D. M. Nekorchuk. 2002. Bartonella-associated endothelial proliferation depends on inhibition of apoptosis. Proc. Natl. Acad. Sci. USA 99:46564661.
65. Koesling, J.,, T. Aebischer,, C. Falch,, R. Schulein, and, C. Dehio. 2001. Cutting edge: antibody-mediated cessation of hemotropic infection by the intraerythrocytic mouse pathogen Bartonella grahamii. J. Immunol. 167:1114.
66. Lavigne, J. P.,, E. Botella, and, D. O’Callaghan. 2006. Type IV secretion system and their effectors: an update. Pathol. Biol. (Paris) 54:296303. (In French.)
67. Locht, C., and, J. M. Keith. 1986. Pertussis toxin gene: nucleotide sequence and genetic organization. Science 232:12581264.
68. Losick, V. P., and, R. R. Isberg. 2006. NFkappaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila. J. Exp. Med. 203:21772189.
69. Luo, Z. Q., and, R. R. Isberg. 2004. Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc. Natl. Acad. Sci. USA 101:841846.
70. Machner, M. P., and, R. R. Isberg. 2006. Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev. Cell 11:4756.
71. Maeda, S.,, M. Otsuka,, Y. Hirata,, Y. Mitsuno,, H. Yoshida,, Y. Shiratori,, Y. Masuho,, M. Muramatsu,, N. Seki, and, M. Omata. 2001. cDNA microarray analysis of Helicobacter pylori-mediated alteration of gene expression in gastric cancer cells. Biochem. Biophys. Res. Commun. 284:443449.
72. Marra, A.,, S. J. Blander,, M. A. Horwitz, and, H. A. Shuman. 1992. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl. Acad. Sci. USA 89:96079611.
73. Masui, S.,, T. Sasaki, and, H. Ishikawa. 2000. Genes for the type IV secretion system in an intra-cellular symbiont, Wolbachia, a causative agent of various sexual alterations in arthropods. J. Bacteriol. 182:65296531.
74. Molmeret, M.,, S. D. Zink,, L. Han,, A. AbuZant,, R. Asari,, D. M. Bitar, and, Y. Abu Kwaik. 2004. Activation of caspase-3 by the Dot/Icm virulence system is essential for arrested biogenesis of the Legionella-containing phagosome. Cell. Microbiol. 6:3348.
75. Molofsky, A. B.,, B. G. Byrne,, N. N. Whit-field,, C. A. Madigan,, E. T. Fuse,, K. Tateda, and, M. S. Swanson. 2006. Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J. Exp. Med. 203:10931104.
76. Moss, J.,, S. J. Stanley,, D. L. Burns,, J. A. Hsia,, D. A. Yost,, G. A. Myers, and, E. L. Hewlett. 1983. Activation by thiol of the latent NAD glycohydrolase and ADPribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein). J. Biol. Chem. 258:1187911882.
77. Murata, T.,, A. Delprato,, A. Ingmundson,, D. K. Toomre,, D. G. Lambright, and, C. R. Roy. 2006. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell Biol. 8:971977.
78. Nagai, H.,, J. C. Kagan,, X. Zhu,, R. A. Kahn, and, C. R. Roy. 2002. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295:679682.
79. Nash, T. W.,, D. M. Libby, and, M. A. Horwitz. 1984. Interaction between the legion-naires’ disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J. Clin. Investig. 74:771782.
80. Nicosia, A.,, M. Perugini,, C. Franzini,, M. C. Casagli,, M. G. Borri,, G. Antoni,, M. Almoni,, P. Neri,, G. Ratti, and, R. Rappuoli. 1986. Cloning and sequencing of the pertussis toxin genes: operon structure and gene duplication. Proc. Natl. Acad. Sci. USA 83:46314635.
81. O’Callaghan, D.,, C. Cazevieille,, A. Allardet-Servent,, M. L. Boschiroli,, G. Bourg,, V. Foulongne,, P. Frutos,, Y. Kulakov, and, M. Ramuz. 1999. A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol. Microbiol. 33:12101220.
82. Odenbreit, S.,, J. Puls,, 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.
83. Ohashi, N.,, N. Zhi,, Q. Lin, and, Y. Rikihisa. 2002. Characterization and transcriptional analysis of gene clusters for a type IV secretion machinery in human granulocytic and monocytic ehrlichiosis agents. Infect. Immun. 70:21282138.
84. Opitz, B.,, M. Vinzing,, V. van Laak,, B. Schmeck,, G. Heine,, S. Gunther,, R. Preissner,, H. Slevogt,, P. D. N’Guessan,, J. Eitel,, T. Goldmann,, A. Flieger,, N. Suttorp, and, S. Hippenstiel. 2006. Legionella pneumophila induced IFNbeta in lung epithelial cells via IPS-1 and IRF3 which also control bacterial replication. J. Biol. Chem. 281:3617336179.
85. Padmalayam, I.,, K. Karem,, B. Baumstark, and, R. Massung. 2000. The gene encoding the 17-kDa antigen of Bartonella henselae is located within a cluster of genes homologous to the virB virulence operon. DNA Cell Biol. 19:377382.
86. Parsonnet, J.,, G. D. Friedman,, D. P. Vandersteen,, Y. Chang,, J. H. Vogelman,, N. Orentreich, and, R. K. Sibley. 1991. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325:11271131.
87. Parsonnet, J.,, S. Hansen,, L. Rodriguez,, A. B. Gelb,, R. A. Warnke,, E. Jellum,, N. Orentreich,, J. H. Vogelman, and, G. D. Friedman. 1994. Helicobacter pylori infection and gastric lymphoma. N. Engl. J. Med. 330:12671271.
88. Purcell, M., and, H. A. Shuman. 1998. The Legionella pneumophila icmGCDJBF genes are required for killing of human macrophages. Infect. Immun. 66:22452255.
89. Ren, T.,, D. S. Zamboni,, C. R. Roy,, W. F. Dietrich, and, R. E. Vance. 2006. Flagellindeficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog. 2:e18.
90. Rieder, G.,, W. Fischer, and, R. Haas. 2005. Interaction of Helicobacter pylori with host cells: function of secreted and translocated molecules. Curr. Opin. Microbiol. 8:6773.
91. Rosenstiel, P.,, S. Hellmig,, J. Hampe,, S. Ott,, A. Till,, W. Fischbach,, H. Sahly,, R. Lucius,, U. R. Folsch,, D. Philpott, and, S. Schreiber. 2006. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cell. Microbiol. 8:11881198.
92. Roux, C. M.,, H. G. Rolan,, R. L. Santos,, P. D. Bereman,, T. L. Thomas,, L. G. Adams, and, R. M. Tsolis. 17 April 2007, posting date. Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice. Cell. Microbiol. doi: 10.1111/j.1462-5822.2007. 00922.x.
93. Salzberg, S. L.,, O. White,, J. Peterson, and, J. A. Eisen. 2001. Microbial genes in the human genome: lateral transfer or gene loss? Science 292:19031906.
94. Schmausser, B.,, C. Josenhans,, S. Endrich,, S. Suerbaum,, C. Sitaru,, M. Andrulis,, S. Brandlein,, P. Rieckmann,, H. K. Muller Hermelink, and, M. Eck. 2004. Downregulation of CXCR1 and CXCR2 expression on human neutrophils by Helicobacter pylori: a new pathomechanism in H. pylori infection? Infect. Immun. 72:67736779.
95. Schmid, M. C.,, F. Scheidegger,, M. Dehio,, N. Balmelle-Devaux,, R. Schulein,, P. Guye,, C. S. Chennakesava,, B. Biedermann, and, C. Dehio. 2006. A translocated bacterial protein protects vascular endothelial cells from apoptosis. PLoS Pathog. 2:e115.
96. Schmid, M. C.,, R. Schulein,, M. Dehio,, G. Denecker,, I. Carena, and, C. Dehio. 2004. The VirB type IV secretion system of Bartonella henselae mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. Mol. Microbiol. 52:8192.
97. Schmiederer, M., and, B. Anderson. 2000. Cloning, sequencing, and expression of three Bartonella henselae genes homologous to the Agrobacterium tumefaciens VirB region. DNA Cell Biol. 19:141147.
98. Schmiederer, M.,, R. Arcenas,, R. Widen,, N. Valkov, and, B. Anderson. 2001. Intra-cellular induction of the Bartonella henselae virB operon by human endothelial cells. Infect. Immun. 69:64956502.
99. Schulein, R., and, C. Dehio. 2002. The VirB/VirD4 type IV secretion system of Bartonella is essential for establishing intraerythrocytic infection. Mol. Microbiol. 46:10531067.
100. Schulein, R.,, P. Guye,, T. A. Rhomberg,, M. C. Schmid,, G. Schroder,, A. C. Vergunst,, I. Carena, and, C. Dehio. 2005. A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells. Proc. Natl. Acad. Sci. USA 102:856861.
101. Schulein, R.,, A. Seubert,, C. Gille,, C. Lanz,, Y. Hansmann,, Y. Piemont, and, C. Dehio. 2001. Invasion and persistent intracellular colonization of erythrocytes. A unique parasitic strategy of the emerging pathogen Bartonella. J. Exp. Med. 193:10771086.
102. 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.
103. Segal, G.,, M. Purcell, and, H. A. Shuman. 1998. Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc. Natl. Acad. Sci. USA 95:16691674.
104. Segal, G.,, J. J. Russo, and, H. A. Shuman. 1999. Relationships between a new type IV secretion system and the icm/dot virulence system of Legionella pneumophila. Mol. Microbiol. 34:799809.
105. Segal, G., and, H. A. Shuman. 1997. Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect. Immun. 65:50575066.
106. Selbach, M.,, S. Moese,, C. R. Hauck,, T. F. Meyer, and, S. Backert. 2002. Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J. Biol. Chem. 277:67756778.
107. Seshadri, R.,, I. T. Paulsen,, J. A. Eisen,, T. D. Read,, K. E. Nelson,, W. C. Nelson,, N. L. Ward,, H. Tettelin,, T. M. Davidsen,, M. J. Beanan,, R. T. Deboy,, S. C. Daugherty,, L. M. Brinkac,, R. Madupu,, R. J. Dodson,, H. M. Khouri,, K. H. Lee,, H. A. Carty,, D. Scanlan,, R. A. Heinzen,, H. A. Thompson,, J. E. Samuel,, C. M. Fraser, and, J. F. Heidelberg. 2003. Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc. Natl. Acad. Sci. USA 100:54555460.
108. Seubert, A.,, R. Hiestand,, F. de la Cruz, and, C. Dehio. 2003. A bacterial conjugation machinery recruited for pathogenesis. Mol. Microbiol. 49:12531266.
109. Sieira, R.,, D. J. Comerci,, D. O. Sanchez, and, R. A. Ugalde. 2000. A homologue of an operon required for DNA transfer in Agrobacterium is required in Brucella abortus for virulence and intracellular multiplication. J. Bacteriol. 182:48494855.
110. Sporri, R.,, N. Joller,, U. Albers,, H. Hilbi, and, A. Oxenius. 2006. MyD88-dependent IFN-γ production by NK cells is key for control of Legionella pneumophila infection. J. Immunol. 176:61626171.
111. 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.
112. Stein, P. E.,, A. Boodhoo,, G. D. Armstrong,, S. A. Cockle,, M. H. Klein, and, R. J. Read. 1994. The crystal structure of pertussis toxin. Structure 2:4557.
113. Stetson, D. B., and, R. Medzhitov. 2006. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 24:93103.
114. Sun, Y. H.,, H. G. Rolan,, A. B. den Hartigh,, D. Sondervan, and, R. M. Tsolis. 2005. Brucella abortus virB12 is expressed during infection but is not an essential component of the type IV secretion system. Infect. Immun. 73:60486054.
115. Tamura, M.,, K. Nogimori,, S. Murai,, M. Yajima,, K. Ito,, T. Katada,, M. Ui, and, S. Ishii. 1982. Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry 21:55165522.
116. Tittarelli, M.,, M. Di Ventura,, F. De Massis,, M. Scacchia,, A. Giovannini,, D. Nannini, and, V. Caporale. 2005. The persistence of Brucella melitensis in experimentally infected ewes through three reproductive cycles. J. Vet. Med. B 52:403409.
117. Viala, J.,, C. Chaput,, I. G. Boneca,, A. Cardona,, S. E. Girardin,, A. P. Moran,, R. Athman,, S. Memet,, M. R. Huerre,, A. J. Coyle,, P. S. DiStefano,, P. J. Sansonetti,, A. Labigne,, J. Bertin,, D. J. Philpott, and, R. L. Ferrero. 2004. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat. Immunol. 5:11661174.
118. Vogel, J. P.,, H. L. Andrews,, S. K. Wong, and, R. R. Isberg. 1998. Conjugative transfer by the virulence system of Legionella pneumophila. Science 279:873876.
119. Weiss, A. A., and, M. S. Goodwin. 1989. Lethal infection by Bordetella pertussis mutants in the infant mouse model. Infect. Immun. 57:37573764.
120. Weiss, A. A.,, E. L. Hewlett,, G. A. Myers, and, S. Falkow. 1984. Pertussis toxin and extra-cytoplasmic adenylate cyclase as virulence factors of Bordetella pertussis. J. Infect. Dis. 150:219222.
121. Weiss, A. A.,, F. D. Johnson, and, D. L. Burns. 1993. Molecular characterization of an operon required for pertussis toxin secretion. Proc. Natl. Acad. Sci. USA 90:29702974.
122. Wilesmith, J. W. 1978. The persistence of Brucella abortus infection in calves: a retrospective study of heavily infected herds. Vet. Rec. 103:149153.
123. Witvliet, M. H.,, D. L. Burns,, M. J. Brennan,, J. T. Poolman, and, C. R. Manclark. 1989. Binding of pertussis toxin to eucaryotic cells and glycoproteins. Infect. Immun. 57:33243330.
124. Wright, E. K.,, S. A. Goodart,, J. D. Growney,, V. Hadinoto,, M. G. Endrizzi,, E. M. Long,, K. Sadigh,, A. L. Abney,, I. Bernstein-Hanley, and, W. F. Dietrich. 2003. Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila. Curr. Biol. 13:2736.
125. Wu, M.,, L. V. Sun,, J. Vamathevan,, M. Riegler,, R. Deboy,, J. C. Brownlie,, E. A. McGraw,, W. Martin,, C. Esser,, N. Ahmadinejad,, C. Wiegand,, R. Madupu,, M. J. Beanan,, L. M. Brinkac,, S. C. Daugherty,, A. S. Durkin,, J. F. Kolonay,, W. C. Nelson,, Y. Mohamoud,, P. Lee,, K. Berry,, M. B. Young,, T. Utterback,, J. Weidman,, W. C. Nierman,, I. T. Paulsen,, K. E. Nelson,, H. Tettelin,, S. L. O’Neill, and, J. A. Eisen. 2004. Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol. 2:e69.
126. Young, E. J. 2000. Brucella species, p. 23862391. In G. L. Mandell,, J. E. Bennett, and, R. Dolin (ed.), Mandell, Douglas and Bennett’s Principles and Practice of Infectious Disease, 5th ed., vol. 2. Churchill Livingstone, Philadelphia, PA.
127. Zamboni, D. S.,, K. S. Kobayashi,, T. Kohlsdorf,, Y. Ogura,, E. M. Long,, R. E. Vance,, K. Kuida,, S. Mariathasan,, V. M. Dixit,, R. A. Flavell,, W. F. Dietrich, and, C. R. Roy. 2006. The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat. Immunol. 7:318325.
128. Zamboni, D. S.,, S. McGrath,, M. Rabinovitch, and, C. R. Roy. 2003. Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system. Mol. Microbiol. 49:965976.


Generic image for table

Animal and human pathogens and endosymbionts encoding T4SS

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15
Generic image for table

Motifs in T4SS effectors with similarity to eukaryotic protein domains

Citation: Roux C, Tsolis R. 2007. Type IV Secretion Systems and Their Role in Eliciting Host Responses to Infection, p 221-237. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch15

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