Chapter 10 : Type IV Secretion Machinery

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This chapter provides an overview of the pathogenic involvement of Type IV secretion systems (T4SS), with a focus on the structural aspects and the molecular mechanisms of the type IV secretion process. The assembled knowledge gained from studies of individual secretion systems is used to propose a unified view of the architecture of the type IV secretion machinery at the molecular level. Different mechanistic aspects are discussed. T4SS are found predominantly in gram-negative bacteria. Exceptions are the bacterial conjugation systems of gram-positive bacteria and archaea with weak homology to the conjugation systems of gram-negative bacteria, which are regarded as the evolutionarily most ancient T4SS. The finding that relaxases are transferred to recipient cells independently of DNA transfer supports the view that the secretion machinery of bacterial conjugation systems transports the relaxase, which in turn trails the DNA and directs it into the target cell. Structural features of relaxases are discussed in the chapter. In T4SS, it is one of the three potential NTPases that are thought to energize the secretion process and/or the assembly of the secretion machinery. Recently, the crystal structures of a family of more widely distributed T4SS substrates, the conjugative relaxases, have been solved. Additionally, the pathway of a T4SS substrate that is always cotransferred with relaxases has been determined. The authors therefore confine themselves to describing the features of conjugative relaxases and the pathway of a relaxase-associated partner molecule, the T-DNA of .

Citation: Schröder G, Savvides S, Waksman G, Lanka E. 2005. Type IV Secretion Machinery, p 179-221. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch10

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Figure 1

Electron microscopic image of P-pili. The image represents a section of an cell producing RP4-encoded P-pili. P-pili (arrowheads) are characteristically long and rigid and thus break off easily from the pilus-producing bacterium. When broken off, they assemble into large, filamentous bundles of pili (indicated by an arrow). Bar, 0.2 µm. This image was taken by Jana Haase and was provided by Gerhild Lüder and Rudi Lurz. Preparation and staining were as described previously ( ), using strain JE2571 harboring plasmids pML123 and pWP471.

Citation: Schröder G, Savvides S, Waksman G, Lanka E. 2005. Type IV Secretion Machinery, p 179-221. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch10
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1. Abrahams, J. P.,, A. G. Leslie,, R. Lutter,, and J. E. Walker. 1994. Structure at 2.8 Å resolution of F1-ATPase from bovine heart mitochondria. Nature 370:621628.
2. Achtman, M.,, G. Morelli,, and S. Schwuchow. 1978. Cell-cell interactions in conjugating Escherichia coli: role of F pili and fate of mating aggregates. J. Bacteriol. 135:10531061.
3. Anderson, B. E.,, J. E. Dawson,, D. C. Jones,, and K. H. Wilson. 1991. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J. Clin. Microbiol. 29:28382842.
4. Anderson, L. B.,, A. V. Hertzel,, and A. Das. 1996. Agrobacterium tumefaciens VirB7 and VirB9 form a disulfide- linked protein complex. Proc. Natl. Acad. Sci. USA 93:88898894.
5. 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.
6. 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.
7. 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.
8. Atmakuri, K.,, Z. Ding,, and P. J. Christie. 2003. VirE2, a type IV secretion substrate, interacts with the VirD4 transfer protein at cell poles of Agrobacterium tumefaciens. Mol. Microbiol. 49:16991713.
9. Azad, A. F.,, and C. B. Beard. 1998. Rickettsial pathogens and their arthropod vectors. Emerg. Infect. Dis. 4:179186.
10. Backert, S.,, Y. Churin,, and T. F. Meyer. 2002. Helicobacter pylori type IV secretion, host cell signalling and vaccine development. Keio J. Med. 51(Suppl. 2):614.
11. Backert, S.,, S. Moese,, M. Selbach,, V. Brinkmann,, and T. F. Meyer. 2001. Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol. Microbiol. 42:631644.
12. Backert, S.,, E. Ziska,, V. Brinkmann,, U. Zimny-Arndt,, A. Fauconnier,, P. R. Jungblut,, 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.
13. Bacon, D. J.,, R. A. Alm,, D. H. Burr,, L. Hu,, D. J. Kopecko,, C. P. Ewing,, T. J. Trust,, and P. Guerry. 2000. Involvement of a plasmid in virulence of Campylobacter jejuni 81-176. Infect. Immun. 68:43844390.
14. Bacon, D. J.,, R. A. Alm,, L. Hu,, T. E. Hickey,, C. P. Ewing,, R. A. Batchelor,, T. J. Trust,, and P. Guerry. 2002. DNA sequence and mutational analyses of the pVir plasmid of Campylobacter jejuni. Infect. Immun. 70:62426250.
15. Balzer, D.,, W. Pansegrau,, and E. Lanka. 1994. Essential motifs of relaxase (TraI) and TraG proteins involved in conjugative transfer of plasmid RP4. J. Bacteriol. 176:42854295.
16. Baron, C.,, M. Llosa,, S. Zhou,, and P. C. Zambryski. 1997a. VirB1, a component of the T-complex transfer machinery of Agrobacterium tumefaciens, is processed to a C-terminal secreted product, VirB1*. J. Bacteriol. 179:12031210.
17. Baron, C.,, Y. R. Thorstenson,, and P. C. Zambryski. 1997b. The lipoprotein VirB7 interacts with VirB9 in the membranes of Agrobacterium tumefaciens. J. Bacteriol. 179:12111218.
18. Bayer, M.,, K. Bischof,, R. Noiges,, and G. Koraimann. 2000. Subcellular localization and processing of the lytic transglycosylase of the conjugative plasmid R1. FEBS Lett. 466:389393.
19. Bayer, M.,, R. Iberer,, K. Bischof,, E. Rassi,, E. Stabentheiner,, G. Zellnig,, and G. Koraimann. 2001. Functional and mutational analysis of p19, a DNA transfer protein with muramidase activity. J. Bacteriol. 183:31763183.
20. Beaupré, C. E.,, J. Bohne,, E. M. Dale,, and A. N. Binns. 1997. Interactions between VirB9 and VirB10 membrane proteins involved in movement of DNA from Agrobacterium tumefaciens into plant cells. J. Bacteriol. 179:7889.
21. Beijersbergen, A.,, A. Den Dulk-Ras,, R. A. Schilperoort,, and P. J. J. Hooykaas. 1992. Conjugative transfer by the virulence system of Agrobacterium tumefaciens. Science 256:13241327.
22. Bell, K. S.,, M. Sebaihia,, L. Pritchard,, M. T. Holden,, L. J. Hyman,, M. C. Holeva,, N. R. Thomson,, S. D. Bentley,, L. J. Churcher,, K. Mungall,, R. Atkin,, N. Bason,, K. Brooks,, T. Chillingworth,, K. Clark,, J. Doggett,, A. Fraser,, Z. Hance,, H. Hauser,, K. Jagels,, S. Moule,, H. Norbertczak,, D. Ormond,, C. Price,, M. A. Quail,, M. Sanders,, D. Walker,, S. Whitehead,, G. P. Salmond,, P. R. Birch,, J. Parkhill,, and I. K. Toth. 2004. Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proc. Natl. Acad. Sci. USA 101:1110511110.
23. Berger, B. R.,, and P. J. Christie. 1993. The Agrobacterium tumefaciens virB4 gene product is an essential virulence protein requiring an intact nucleoside triphosphate-binding domain. J. Bacteriol. 175:17231734.
24. Berger, B. R.,, and P. J. Christie. 1994. Genetic complementation analysis of the Agrobacterium tumefaciens virB operon: virB2 through virB11 are essential virulence genes. J. Bacteriol. 176:36463660.
25. 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.
26. Binns, A. N.,, and P. Costantino,. 1998. The Agrobacterium oncogenes, p. 251266. In H. P. Spaink,, A. Kondorosi,, and P. J. J. Hooykaas (ed.), The Rhizobiaceae:Molecular Biology of Model Plant-Associated Bacteria. Kluwer Academic Publishers, Dordrecht, The Netherlands.
27. Bohne, J.,, A. Yim,, and A. N. Binns. 1998. The Ti plasmid increases the efficiency of Agrobacterium tumefaciens as a recipient in virB-mediated conjugal transfer of an IncQ plasmid. Proc. Natl. Acad. Sci. USA 95:70577062.
28. Bolland, S.,, M. Llosa,, P. Avila,, and F. de la Cruz. 1990. General organization of the conjugal transfer genes of the IncW plasmid R388 and interactions between R388 and IncN and IncP plasmids. J. Bacteriol. 172:57955802.
29. Boschiroli, M. L.,, V. Foulongne,, and D. O’Callaghan. 2001. Brucellosis: a worldwide zoonosis. Curr. Opin. Microbiol. 4:5864.
30. Bradley, D. E.,, J. N. Coetzee,, and R. W. Hedges. 1983. IncI2 plasmids specify sensitivity to filamentous bacteriophage IKe. J. Bacteriol. 154:505507.
31. 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.
32. Breitschwerdt, E. B.,, and D. L. Kordick. 2000. Bartonella infection in animals: carriership, reservoir potential, pathogenicity, and zoonotic potential for human infection. Clin. Microbiol. Rev. 13:428438.
33. Buell, C. R.,, V. Joardar,, M. Lindeberg,, J. Selengut,, I. T. Paulsen,, M. L. Gwinn,, R. J. Dodson,, R. T. Deboy,, A. S. Durkin,, J. F. Kolonay,, R. Madupu,, S. Daugherty,, L. Brinkac,, M. J. Beanan,, D. H. Haft,, W. C. Nelson,, T. Davidsen,, N. Zafar,, L. Zhou,, J. Liu,, Q. Yuan,, H. Khouri,, N. Fedorova,, B. Tran,, D. Russell,, K. Berry,, T. Utterback,, S. E. Van Aken,, T. V. Feldblyum,, M. D’Ascenzo,, W. L. Deng,, A. R. Ramos,, J. R. Alfano,, S. Cartinhour,, A. K. Chatterjee,, T. P. Delaney,, S. G. Lazarowitz,, G. B. Martin,, D. J. Schneider,, X. Tang,, C. L. Bender,, O. White,, C. M. Fraser,, and A. Collmer. 2003. The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000. Proc. Natl. Acad. Sci. USA 100:1018110186.
34. Buhrdorf, R.,, C. Förster,, R. Haas,, and W. Fischer. 2003. Topological analysis of a putative virB8 homologue essential for the cag type IV secretion system in Helicobacter pylori. Int. J. Med. Microbiol. 293:213217.
35. Bundock, P.,, A. den Dulk-Ras,, A. Beijersbergen,, and P. J. J. Hooykaas. 1995. Trans-kingdom T-DNA transfer from Agrobacterium tumefaciens to Saccharomyces cerevisiae. EMBO J. 14:32063214.
36. Büttner, D.,, and U. Bonas. 2002. Getting across—bacterial type III effector proteins on their way to the plant cell. EMBO J. 21:53135322.
37. Cabezón, E.,, E. Lanka,, and F. de la Cruz. 1994. Requirements for mobilization of plasmids RSF1010 and ColE1 by the IncW plasmid R388: trwB and RP4 traG are interchangeable. J. Bacteriol. 176:44554458.
38. Cabezón, E.,, J. I. Sastre,, and F. de la Cruz. 1997. Genetic evidence of a coupling role for the TraG protein family in bacterial conjugation. Mol. Gen. Genet. 254:400406.
39. Campos-Olivas, R.,, J. M. Louis,, D. Clérot,, B. Gronenborn,, and A. M. Gronenborn. 2002. The structure of a replication initiator unites diverse aspects of nucleic acid metabolism. Proc. Natl. Acad. Sci. USA 99:1031010315.
40. Cascales, E.,, and P. J. Christie. 2003. The versatile bacterial type IV secretion systems. Nat. Rev. Microbiol. 1:137149.
41. Cascales, E.,, and P. J. Christie. 2004. Definition of a bacterial type IV secretion pathway for a DNA substrate. Science 304:11701173.
42. Celli, J.,, C. de Chastellier,, D. M. Franchini,, 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.
43. 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.
44. Charpentier, E.,, G. Gerbaud,, and P. Courvalin. 1999. Conjugative mobilization of the rolling-circle plasmid pIP823 from Listeria monocytogenes BM4293 among gram-positive and gram-negative bacteria. J. Bacteriol. 181:33683374.
45. 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.
46. Chen, L.,, Y. Chen,, D. W. Wood,, and E. W. Nester. 2002. A new type IV secretion system promotes conjugal transfer in Agrobacterium tumefaciens. J. Bacteriol. 184:48384845.
47. Chen, S. M.,, J. S. Dumler,, J. S. Bakken,, and D. H. Walker. 1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J. Clin. Microbiol. 32:589595.
48. Chen, Y. C.,, S. C. Chang,, K. T. Luh,, and W. C. Hsieh. 1991. Actinobacillus actinomycetemcomitans endocarditis: a report of four cases and review of the literature. Q. J. Med. 81:871878.
49. 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.
50. Christie, P. J.,, J. E. Ward, Jr.,, M. P. Gordon,, and E. W. Nester. 1989. A gene required for transfer of T-DNA to plants encodes an ATPase with autophosphorylating activity. Proc. Natl. Acad. Sci. USA 86:96779681.
51. Churin, Y.,, E. Kardalinou,, T. F. Meyer,, and M. Naumann. 2001. Pathogenicity island-dependent activation of Rho GTPases Rac1 and Cdc42 in Helicobacter pylori infection. Mol. Microbiol. 40:815823.
52. Citovsky, V.,, M. L. Wong,, and P. Zambryski. 1989. Cooperative interaction of Agrobacterium VirE2 protein with single-stranded DNA: implications for the T-DNA transfer process. Proc. Natl. Acad. Sci. USA 86:11931197.
53. Citovsky, V.,, J. Zupan,, D. Warnick,, and P. Zambryski. 1992. Nuclear localization of Agrobacterium VirE2 protein in plant cells. Science 256:18021805.
54. Comerci, D. J.,, M. J. Martínez-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.
55. Conover, G. M.,, I. Derre,, J. P. Vogel,, and R. R. Isberg. 2003. The Legionella pneumophila LidA protein: a translocated substrate of the Dot/Icm system associated with maintenance of bacterial integrity. Mol. Microbiol. 48:305321.
56. Cook, D. M.,, K. M. Farizo,, and D. L. Burns. 1999. Identification and characterization of PtlC, an essential component of the pertussis toxin secretion system. Infect. Immun. 67:754759.
57. Corbel, M. J. 1997. Brucellosis: an overview. Emerg. Infect. Dis. 3:213221.
58. Cornelis, G. R.,, and F. Van Gijsegem. 2000. Assembly and function of type III secretory systems. Annu. Rev. Microbiol. 54:735774.
59. Crabtree, J. E.,, Z. Xiang,, I. J. Lindley,, D. S. Tompkins,, R. Rappuoli,, and A. Covacci. 1995. Induction of interleukin- 8 secretion from gastric epithelial cells by a cagA negative isogenic mutant of Helicobacter pylori. J. Clin. Pathol. 48:967969.
60. Craig-Mylius, K. A.,, and A. A. Weiss. 1999. Mutants in the ptlA-H genes of Bordetella pertussis are deficient for pertussis toxin secretion. FEMS Microbiol. Lett. 179:479484.
61. Dang, T. A.,, and P. J. Christie. 1997. The VirB4 ATPase of Agrobacterium tumefaciens is a cytoplasmic membrane protein exposed at the periplasmic surface. J. Bacteriol. 179:453462.
62. Dang, T. A.,, X. R. Zhou,, B. Graf,, and P. J. Christie. 1999. Dimerization of the Agrobacterium tumefaciens VirB4 ATPase and the effect of ATP-binding cassette mutations on the assembly and function of the T-DNA transporter. Mol. Microbiol. 32:12391253.
63. Das, A.,, and Y. H. Xie. 1998. Construction of transposon Tn3phoA: its application in defining the membrane topology of the Agrobacterium tumefaciens DNA transfer proteins. Mol. Microbiol. 27:405414.
64. Das, A.,, and Y. H. Xie. 2000. The Agrobacterium T-DNA transport pore proteins VirB8, VirB9, and VirB10 interact with one another. J. Bacteriol. 182:758763.
65. daSilva, A. C.,, J. A. Ferro,, F. C. Reinach,, C. S. Farah,, L. R. Furlan,, R. B. Quaggio,, C. B. Monteiro- Vitorello,, M. A. VanSluys,, N. F. Almeida,, L. M. Alves,, A. M. do Amaral,, M. C. Bertolini,, L. E. Camargo,, G. Camarotte,, F. Cannavan,, J. Cardozo,, F. Chambergo,, L. P. Ciapina,, R. M. Cicarelli,, L. L. Coutinho,, J. R. Cursino-Santos,, H. El Dorry,, J. B. Faria,, A. J. Ferreira,, R. C. Ferreira,, M. I. Ferro,, E. F. Formighieri,, M. C. Franco,, C. C. Greggio,, A. Gruber,, A. M. Katsuyama,, L. T. Kishi,, R. P. Leite,, E. G. Lemos,, M. V. Lemos,, E. C. Locali,, M. A. Machado,, A. M. Madeira,, N. M. Martinez-Rossi,, E. C. Martins,, J. Meidanis,, C. F. Menck,, C. Y. Miyaki,, D. H. Moon,, L. M. Moreira,, M. T. Novo,, V. K. Okura,, M. C. Oliveira,, V. R. Oliveira,, H. A. Pereira,, A. Rossi,, J. A. Sena,, C. Silva,, R. F. deSouza,, L. A. Spinola,, M. A. Takita,, R. E. Tamura,, E. C. Teixeira,, R. I. Tezza,, M. TrindadedosSantos,, D. Truffi,, S. M. Tsai,, F. F. White,, J. C. Setubal,, and J. P. Kitajima. 2002. Comparison of the genomes of two Xanthomonas pathogens with differing host specificities. Nature 417:459463.
66. Datta, S.,, C. Larkin,, and J. F. Schildbach,. 2003. Structural insights into single-stranded DNA binding and cleavage by F factor TraI. Structure 11:13691379.
67. de Groot, M. J.,, P. Bundock,, P. J. J. Hooykaas,, and A. G. Beijersbergen. 1998. Agrobacterium tumefaciensmediated transformation of filamentous fungi. Nat. Biotechnol. 16:839842.
68. Dehio, C. 2001. Bartonella interactions with endothelial cells and erythrocytes. Trends Microbiol. 9:279285.
69. Dehio, C. 2003. Recent progress in understanding Bartonella-induced vascular proliferation. Curr. Opin. Microbiol. 6:6165.
70. Dehio, C. 2004. Molecular and cellular basis of Bartonella pathogenesis. Annu. Rev. Microbiol. 58:365390.
71. 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.
72. de la Cruz, F.,, and E. Lanka,. 1998. Function of the Ti-plasmid Vir proteins: T-complex formation and transfer to the plant cell, p. 281301. In H. P. Spaink,, A. Kondorosi,, and P. J. J. Hooykaas (ed.), The Rhizobiaceae: Molecular Biology of Model Plant-Associated Bacteria. Kluwer Academic Publishers, Dordrecht, The Netherlands.
73. Delrue, R. M.,, M. Martínez-Lorenzo,, P. Lestrate,, I. Danese,, V. Bielarz,, P. Mertens,, B. De, X, A. Tibor, J. P. Gorvel, and J. J. Letesson. 2001. Identification of Brucella spp. genes involved in intracellular trafficking. Cell. Microbiol. 3:487497.
74. Deng, W.,, and E. W. Nester,. 1998. Determinants of host specificity of Agrobacterium and their function, p. 321338. In H. P. Spaink,, A. Kondorosi,, and P. J. J. Hooykaas (eds.), The Rhizobiaceae:Molecular Biology of Model Plant-Associated Bacteria. Kluwer Academic Publishers, Dordrecht, The Netherlands.
75. Dillard, J. P.,, and H. S. Seifert. 2001. A variable genetic island specific for Neisseria gonorrhoeae is involved in providing DNA for natural transformation and is found more often in disseminated infection isolates. Mol. Microbiol. 41:263277.
76. Ding, Z.,, K. Atmakuri,, and P. J. Christie. 2003. The outs and ins of bacterial type IV secretion substrates. Trends Microbiol. 11:527535.
77. Disqué-Kochem, C.,, and B. Dreiseikelmann. 1997. The cytoplasmic DNA-binding protein TraM binds to the inner membrane protein TraD in vitro. J. Bacteriol. 179:61336137.
78. Duckely, M.,, and B. Hohn. 2003. The VirE2 protein of Agrobacterium tumefaciens: the Yin and Yang of T-DNA transfer. FEMS Microbiol. Lett. 223:16.
79. Eisenbrandt, R.,, M. Kalkum,, E. M. Lai,, R. Lurz,, C. I. Kado,, and E. Lanka. 1999. Conjugative pili of IncP plasmids, and the Ti plasmid T pilus are composed of cyclic subunits. J. Biol. Chem. 274:2254822555.
80. Eisenbrandt, R.,, M. Kalkum,, R. Lurz,, and E. Lanka. 2000. Maturation of IncP pilin precursors resembles the catalytic dyad-like mechanism of leader peptidases. J. Bacteriol. 182:67516761.
81. 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.
82. Fernandez, D.,, T. A. Dang,, G. M. Spudich,, X. R. Zhou,, B. R. Berger,, and P. J. Christie. 1996b. The Agrobacterium tumefaciens virB7 gene product, a proposed component of the T-complex transport apparatus, is a membrane-associated lipoprotein exposed at the periplasmic surface. J. Bacteriol. 178:31563167.
83. Fernandez, D.,, G. M. Spudich,, X. R. Zhou,, and P. J. Christie. 1996a. The Agrobacterium tumefaciens VirB7 lipoprotein is required for stabilization of VirB proteins during assembly of the T-complex transport apparatus. J. Bacteriol. 178:31683176.
84. Fields, B. S.,, R. F. Benson,, and R. E. Besser. 2002. Legionella and Legionnaires’ disease: 25 years of investigation. Clin. Microbiol. Rev. 15:506526.
85. Finberg, K. E.,, T. R. Muth,, S. P. Young,, J. B. Maken,, S. M. Heitritter,, A. N. Binns,, and L. M. Banta. 1995. Interactions of VirB9, -10, and -11 with the membrane fraction of Agrobacterium tumefaciens: solubility studies provide evidence for tight associations. J. Bacteriol. 177:48814889.
86. Fischer, W.,, J. Püls,, R. Buhrdorf,, B. Gebert,, S. Odenbreit,, and R. Haas. 2001. Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol. Microbiol. 42:13371348.
87. Freiberg, C.,, R. Fellay,, A. Bairoch,, W. J. Broughton,, A. Rosenthal,, and X. Perret. 1997. Molecular basis of symbiosis between Rhizobium and legumes. Nature 387:394401.
88. Frost, L. S., 1993. Conjugative pili and pilus-specific phages, p. 189221. In D. B. Clewell (ed.), Bacterial Conjugation. Plenum Press, New York, N.Y.
89. Fullner, K. J.,, J. C. Lara,, and E. W. Nester. 1996. Pilus assembly by Agrobacterium T-DNA transfer genes. Science 273:11071109.
90. Fullner, K. J.,, K. M. Stephens,, and E. W. Nester. 1994. An essential virulence protein of Agrobacterium tumefaciens, VirB4, requires an intact mononucleotide binding domain to function in transfer of T-DNA. Mol. Gen. Genet. 245:704715.
91. Gao, L. Y.,, and K. Y. Abu. 1999a. Activation of caspase 3 during Legionella pneumophila-induced apoptosis. Infect. Immun. 67:48864894.
92. Gao, L. Y.,, and K. Y. Abu. 1999b. Apoptosis in macrophages and alveolar epithelial cells during early stages of infection by Legionella pneumophila and its role in cytopathogenicity. Infect. Immun. 67:862870.
93. Gao, L. Y.,, and Y. A. Kwaik. 2000. The modulation of host cell apoptosis by intracellular bacterial pathogens. Trends Microbiol. 8:306313.
94. Gelvin, S. B. 2003. Agrobacterium-mediated plant transformation: the biology behind the “gene-jockeying” tool. Microbiol. Mol. Biol. Rev. 67:1637.
95. Gilman, A. G. 1987. G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56:615649.
96. Gilmour, M. W.,, J. E. Gunton,, T. D. Lawley,, and D. E. Taylor. 2003. Interaction between the IncHI1 plasmid R27 coupling protein and type IV secretion system: TraG associates with the coiled-coil mating pair formation protein TrhB. Mol. Microbiol. 49:105116.
97. Gilmour, M. W.,, T. D. Lawley,, M. M. Rooker,, P. J. Newnham,, and D. E. Taylor. 2001. Cellular location and temperature-dependent assembly of IncHI1 plasmid R27-encoded TrhC-associated conjugative transfer protein complexes. Mol. Microbiol. 42:705715.
98. Gilmour, M. W.,, and D. E. Taylor. 2004. A subassembly of R27-encoded transfer proteins is dependent on TrhC nucleoside triphosphate-binding motifs for function but not formation. J. Bacteriol. 186:16061613.
99. Gomis-Rüth, F. X.,, and M. Coll. 2001. Structure of TrwB, a gatekeeper in bacterial conjugation. Int. J. Biochem. Cell Biol. 33:839843.
100. Gomis-Rüth, F. X.,, G. Moncalián,, F. de la Cruz,, and M. Coll. 2002. Conjugative plasmid protein TrwB, an integral membrane type IV secretion system coupling protein. Detailed structural features and mapping of the active site cleft. J. Biol. Chem. 277:75567566.
101. Gomis-Rüth, F. X.,, G. Moncalián,, R. Pérez-Luque,, A. González,, E. Cabezón,, F. de la Cruz,, and M. Coll. 2001. The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase. Nature 409:637641.
102. Goodner, B.,, G. Hinkle,, S. Gattung,, N. Miller,, M. Blanchard,, B. Qurollo,, B. S. Goldman,, Y. Cao,, M. Askenazi,, C. Halling,, L. Mullin,, K. Houmiel,, J. Gordon,, M. Vaudin,, O. Iartchouk,, A. Epp,, F. Liu,, C. Wollam,, M. Allinger,, D. Doughty,, C. Scott,, C. Lappas,, B. Markelz,, C. Flanagan,, C. Crowell,, J. Gurson,, C. Lomo,, C. Sear,, G. Strub,, C. Cielo,, and S. Slater. 2001. Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58. Science 294:23232328.
103. Gormley, E. P.,, and J. Davis. 1991. Transfer of plasmid RSF1010 by conjugation from Escherichia coli to Streptomyces lividans and Mycobacterium smegmatis. J. Bacteriol. 173:67056708.
104. Gorvel, J. P.,, and E. Moreno. 2002. Brucella intracellular life: from invasion to intracellular replication. Vet. Microbiol. 90:281297.
105. Grahn, A. M.,, J. Haase,, D. H. Bamford,, and E. Lanka. 2000. Components of the RP4 conjugative transfer apparatus form an envelope structure bridging inner and outer membranes of donor cells: implications for related macromolecule transport systems. J. Bacteriol. 182:15641574.
106. Grandoso, G.,, P. Avila,, A. Cayón,, M. A. Hernando,, M. Llosa,, and F. de la Cruz. 2000. Two active-site tyrosyl residues of protein TrwC act sequentially at the origin of transfer during plasmid R388 conjugation. J. Mol. Biol. 295:11631172.
107. Grohmann, E.,, G. Muth,, and M. Espinosa. 2003. Conjugative plasmid transfer in gram-positive bacteria. Microbiol. Mol. Biol. Rev. 67:277301.
108. Guasch, A.,, M. Lucas,, G. Moncalián,, M. Cabezas,, R. Pérez-Luque,, F. X. Gomis-Rüth,, F. de la Cruz,, and M. Coll. 2003. Recognition and processing of the origin of transfer DNA by conjugative relaxase TrwC. Nat. Struct. Biol. 10:10021010.
109. Haase, J.,, R. Lurz,, A. M. Grahn,, D. H. Bamford,, and E. Lanka. 1995. Bacterial conjugation mediated by plasmid RP4: donor-specific phage propagation, RSF1010 mobilization and pili production require the same Tra2 core components of a proposed DNA transport structure. J. Bacteriol. 177:47794791.
110. Hamilton, C. M.,, H. Lee,, P. L. Li,, D. M. Cook,, K. R. Piper,, S. B. von Bodman,, E. Lanka,, W. Ream,, and S. K. Farrand. 2000. TraG from RP4 and TraG and VirD4 from Ti plasmids confer relaxosome specificity to the conjugal transfer system of pTiC58. J. Bacteriol. 182:15411548.
111. Hamori, P. J.,, and T. G. Slama. 1989. Actinobacillus prosthetic valve endocarditis. Am. Heart J. 118:853854.
112. Hanai, R.,, and J. C. Wang. 1993. The mechanism of sequence-specific DNA cleavage and strand transfer by ϕX174 gene A∗ protein. J. Biol. Chem. 268:2383023836.
113. Hapfelmeier, S.,, N. Domke,, P. C. Zambryski,, and C. Baron. 2000. VirB6 is required for stabilization of VirB5 and VirB3 and formation of VirB7 homodimers in Agrobacterium tumefaciens. J. Bacteriol. 182:45054511.
114. Harley, M. J.,, and J. F. Schildbach. 2003. Swapping single-stranded DNA sequence specificities of relaxases from conjugative plasmids F and R100. Proc. Natl. Acad. Sci. USA 100:1124311248.
115. Harris, R. L.,, V. Hombs,, and P. M. Silverman. 2001. Evidence that F-plasmid proteins TraV, TraK, and TraB assemble into an envelope-spanning structure in Escherichia coli. Mol. Microbiol. 42:757766.
116. Heinemann, J. A.,, and G. F. Sprague, Jr. 1989. Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast. Nature 340:205209.
117. Hickey, T. E.,, A. L. McVeigh,, D. A. Scott,, R. E. Michielutti,, A. Bixby,, S. A. Carroll,, A. L. Bourgeois,, and P. Guerry. 2000. Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells. Infect. Immun. 68:65356541.
118. Hickman, A. B.,, D. R. Ronning,, R. M. Kotin,, and F. Dyda. 2002. Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep. Mol. Cell 10:327337.
119. Higashi, H.,, R. Tsutsumi,, S. Muto,, T. Sugiyama,, T. Azuma,, M. Asaka,, and M. Hatakeyama. 2002a. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295:683686.
120. Higashi, H.,, R. Tsutsumi,, A. Fujita,, S. Yamazaki,, M. Asaka,, T. Azuma,, and M. Hatakeyama. 2002b. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc. Natl. Acad. Sci. USA 99:1442814433.
121. 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.
122. Hormaeche, I.,, I. Alkorta,, F. Moro,, J. M. Valpuesta,, F. M. Goñi,, and F. de la Cruz. 2002. Purification and properties of TrwB, a hexameric, ATP-binding integral membrane protein essential for R388 plasmid conjugation. J. Biol. Chem. 277:4645646462.
123. Horwitz, M. A. 1983. The Legionnaires’ disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J. Exp. Med. 158:21082126.
124. Houdusse, A.,, A. G. Szent-Györgyi,, and C. Cohen. 2000. Three conformational states of scallop myosin S1. Proc. Natl. Acad. Sci. USA 97:1123811243.
125. Howard, E. A.,, B. A. Winsor,, G. De Vos,, and P. Zambryski. 1989. Activation of the T-DNA transfer process in Agrobacterium results in the generation of a T-strand-protein complex: tight association of VirD2 with the 5' ends of T-strands. Proc. Natl. Acad. Sci. USA 86:40174021.
126. Howard, E. A.,, J. R. Zupan,, V. Citovsky,, and P. C. Zambryski. 1992. The VirD2 protein of A. tumefaciens contains a C-terminal bipartite nuclear localization signal: implications for nuclear uptake of DNA in plant cells. Cell 68:109118.
127. Hwang, B. J.,, K. M. Woo,, A. L. Goldberg,, and C. H. Chung. 1988. Protease Ti, a new ATP-dependent protease in Escherichia coli, contains protein-activated ATPase and proteolytic functions in distinct subunits. J. Biol. Chem. 263:87278734.
128. Jakubowski, S. J.,, V. Krishnamoorthy,, E. Cascales,, and P. J. Christie. 2004. Agrobacterium tumefaciens VirB6 domains direct the ordered export of a DNA substrate through a type IV secretion system. J. Mol. Biol. 341:961977.
129. Jakubowski, S. J.,, V. Krishnamoorthy,, and P. J. Christie. 2003. Agrobacterium tumefaciensVirB6 protein participates in formation of VirB7 and VirB9 complexes required for type IV secretion. J. Bacteriol. 185:28672878.
130. Johnson, T. M.,, and A. Das,. 1998. Organization and regulation of expression of the Agrobacterium virulence genes, p. 267279. In H. P. Spaink,, A. Kondorosi,, and P. J. J. Hooykaas (ed.), The Rhizobiaceae: Molecular Biology of Model Plant-Associated Bacteria. Kluwer Academic Publishers, Dordrecht, The Netherlands.
131. Jones, A. L.,, K. Shirasu,, and C. I. Kado. 1994. The product of the virB4 gene of Agrobacterium tumefaciens promotes accumulation of VirB3 protein. J. Bacteriol. 176:52555261.
132. Kalkum, M.,, R. Eisenbrandt,, R. Lurz,, and E. Lanka. 2002. Tying rings for sex. Trends Microbiol. 10:382387.
133. Karem, K. L.,, C. D. Paddock,, and R. L. Regnery. 2000. Bartonella henselae, B. quintana, and B. bacilliformis: historical pathogens of emerging significance. Microbes. Infect. 2:11931205.
134. Katada, T.,, M. Tamura,, and M. Ui. 1983. The A protomer of islet-activating protein, pertussis toxin, as an active peptide catalyzing ADP-ribosylation of a membrane protein. Arch. Biochem. Biophys. 224:290298.
135. 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.
136. Kerr, A., 1992. The genus Agrobacterium, p. 22142235. In K. Balows (ed.), The Prokaryotes, vol. III, Springer- Verlag KG, Berlin, Germany.
137. Konkel, M. E.,, B. J. Kim,, V. Rivera-Amill,, and S. G. Garvis. 1999. Bacterial secreted proteins are required for the internalization of Campylobacter jejuni into cultured mammalian cells. Mol. Microbiol. 32:691701.
138. Koraimann, G. 2003. Lytic transglycosylases in macromolecular transport systems of Gram-negative bacteria. Cell Mol. Life Sci. 60:23712388.
139. Kotilainen, M. M.,, A. M. Grahn,, J. K. Bamford,, and D. H. Bamford. 1993. Binding of an Escherichia coli double-stranded DNA virus PRD1 to a receptor coded by an IncP-type plasmid. J. Bacteriol. 175:30893095.
140. Krall, L.,, U. Wiedemann,, G. Unsin,, S. Weiss,, N. Domke,, and C. Baron. 2002. Detergent extraction identifies different VirB protein subassemblies of the type IV secretion machinery in the membranes of Agrobacterium tumefaciens. Proc. Natl. Acad. Sci. USA 99:1140511410.
141. Krause, S.,, M. Bárcena,, W. Pansegrau,, R. Lurz,, J. M. Carazo,, and E. Lanka. 2000a. Sequence-related protein export NTPases encoded by the conjugative transfer region of RP4 and by the cag pathogenicity island of Helicobacter pylori share similar hexameric ring structures. Proc. Natl. Acad. Sci. USA 97:30673072.
142. Krause, S.,, W. Pansegrau,, R. Lurz,, F. de la Cruz,, and E. Lanka. 2000b. Enzymology of type IV macromolecule secretion systems: the conjugative transfer regions of plasmids RP4 and R388 and the cag pathogenicity island of Helicobacter pylori encode structurally and functionally related nucleoside triphosphate hydrolases. J. Bacteriol. 182:27612770.
143. Kumar, R. B.,, and A. Das. 2001. Functional analysis of the Agrobacterium tumefaciens T-DNA transport pore protein VirB8. J. Bacteriol. 183:36363641.
144. Kumar, R. B.,, and A. Das. 2002. Polar location and functional domains of the Agrobacterium tumefaciens DNA transfer protein VirD4. Mol. Microbiol. 43:15231532.
145. Kumar, R. B.,, Y. H. Xie,, and A. Das. 2000. Subcellular localization of the Agrobacterium tumefaciens T-DNA transport pore proteins: VirB8 is essential for the assembly of the transport pore. Mol. Microbiol. 36:608617.
146. Kunik, T.,, T. Tzfira,, Y. Kapulnik,, Y. Gafni,, C. Dingwall,, and V. Citovsky. 2001. Genetic transformation of HeLa cells by Agrobacterium. Proc. Natl. Acad. Sci. USA 98:18711876.
147. Kurenbach, B.,, C. Bohn,, J. Prabhu,, M. Abudukerim,, U. Szewzyk,, and E. Grohmann. 2003. Intergeneric transfer of the Enterococcus faecalis plasmid pIP501 to Escherichia coli and Streptomyces lividans and sequence analysis of its tra region. Plasmid 50:8693.
148. Lai, E. M.,, and C. I. Kado. 1998. Processed VirB2 is the major subunit of the promiscuous pilus of Agrobacterium tumefaciens. J. Bacteriol. 180:27112717.
149. Lai, E. M.,, and C. I. Kado. 2000. The T-pilus of Agrobacterium tumefaciens. Trends Microbiol. 8:361369.
150. Lederberg, J.,, and E. Tatum. 1946. Gene recombination in E. coli. Nature 158:558.
151. Lee, M. H.,, N. Kosuk,, J. Bailey,, B. Traxler,, and C. Manoil. 1999. Analysis of F factor TraD membrane topology by use of gene fusions and trypsin-sensitive insertions. J. Bacteriol. 181:61086113.
152. Lenzen, C. U.,, D. Steinmann,, S. W. Whiteheart,, and W. I. Weis. 1998. Crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein. Cell 94:525536.
153. Lessl, M.,, W. Pansegrau,, and E. Lanka. 1992a. Relationship of DNA-transfer-systems: essential transfer factors of plasmids RP4, Ti and F share common sequences. Nucleic Acids Res. 20:60996100.
154. Lessl, M.,, D. Balzer,, R. Lurz,, V. L. Waters,, D. G. Guiney,, and E. Lanka. 1992b. Dissection of IncP conjugative plasmid transfer: definition of the transfer region Tra2 by mobilization of the Tra1 region in trans. J. Bacteriol. 174:24932500.
155. Lessl, M.,, D. Balzer,, K. Weyrauch,, and E. Lanka. 1993. The mating pair formation system of plasmid RP4 defined by RSF1010 mobilization and donor-specific phage propagation. J. Bacteriol. 175:64156425.
156. Lessl, M.,, and E. Lanka. 1994. Common mechanisms in bacterial conjugation and Ti-mediated T-DNA transfer to plant cells. Cell 77:321324.
157. Li, P. L.,, D. M. Everhart,, and S. K. Farrand. 1998. Genetic and sequence analysis of the pTiC58 trb locus, encoding a mating-pair formation system related to members of the type IV secretion family. J. Bacteriol. 180:61646172.
158. Lilley, A.,, P. Young,, and M. Bailey,. 2000. Bacterial population genetics: do plasmids maintain bacterial diversity and adaptation? p. 287300. In C. M. Thomas (ed.), The Horizontal Gene Pool. Harwood Academic Publishers, Amsterdam, The Netherlands.
159. Liu, Z.,, and A. N. Binns. 2003. Functional subsets of the virB type IV transport complex proteins involved in the capacity of Agrobacterium tumefaciens to serve as a recipient in virB-mediated conjugal transfer of plasmid RSF1010. J. Bacteriol. 185:32593269.
160. Llosa, M.,, S. Bolland,, and F. de la Cruz. 1994. Genetic organization of the conjugal DNA processing region of the IncW plasmid R388. J. Mol. Biol. 235:448464.
161. Llosa, M.,, and F. de la Cruz. 2005. Bacterial conjugation: a potential tool for genomic engineering. Res. Microbiol. 156:16.
162. Llosa, M.,, F. X. Gomis-Rüth,, M. Coll,, and F. de la Cruz. 2002. Bacterial conjugation: a two-step mechanism for DNA transport. Mol. Microbiol. 45:18.
163. Llosa, M.,, G. Grandoso,, M. A. Hernando,, and F. de la Cruz. 1996. Functional domains in protein TrwC of plasmid R388: dissected DNA strand transferase and DNA helicase activities reconstitute protein function. J. Mol. Biol. 264:5667.
164. Llosa, M.,, S. Zunzunegui,, and F. de la Cruz. 2003. Conjugative coupling proteins interact with cognate and heterologous VirB10-like proteins while exhibiting specificity for cognate relaxosomes. Proc. Natl. Acad. Sci. USA 100:1046510470.
165. Llosa, M.,, J. Zupan,, C. Baron,, and P. Zambryski. 2000. The N- and C-terminal portions of the Agrobacterium VirB1 protein independently enhance tumorigenesis. J. Bacteriol. 182:34373445.
166. Locht, C.,, and J. M. Keith. 1986. Pertussis toxin gene: nucleotide sequence and genetic organization. Science 232:12581264.
167. 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.
168. Lybarger, R. L.,, and M. Sandkvist. 2004. A hitchhiker’s guide to type IV secretion. Science 304:11221123.
169. Machón, C.,, S. Rivas,, A. Albert,, F. M. Goñi,, and F. de la Cruz. 2002. TrwD, the hexameric traffic ATPase encoded by plasmid R388, induces membrane destabilization and hemifusion of lipid vesicles. J. Bacteriol. 184:16611668.
170. Maeno, N.,, H. Oda,, K. Yoshiie,, M. R. Wahid,, T. Fujimura,, and S. Matayoshi. 1999. Live Bartonella henselae enhances endothelial cell proliferation without direct contact. Microb. Pathog. 27:419427.
171. Malek, J. A.,, J. M. Wierzbowski,, W. Tao,, S. A. Bosak,, D. J. Saranga,, L. Doucette-Stamm,, D. R. Smith,, P. J. McEwan,, and K. J. McKernan. 2004. Protein interaction mapping on a functional shotgun sequence of Rickettsia sibirica. Nucleic Acids Res. 32:10591064.
172. Manders, S. M. 1996. Bacillary angiomatosis. Clin. Dermatol. 14:295299.
173. Marques, M. V.,, A. M. da Silva,, and S. L. Gomes. 2001. Genetic organization of plasmid pXF51 from the plant pathogen Xylella fastidiosa. Plasmid 45:184199.
174. Martin, B. F.,, B. M. Derby,, G. N. Budzilovich,, and J. Ransohoff. 1967. Brain abscess due to Actinobacillus actinomycetemcomitans. Neurology 17:833837.
175. Masui, S.,, T. Sasaki,, and H. Ishikawa. 2000. Genes for the type IV secretion system in an intracellular symbiont, Wolbachia, a causative agent of various sexual alterations in arthropods. J. Bacteriol. 182:65296531.
176. Matson, S. W.,, J. K. Sampson,, and D. R. Byrd. 2001. F plasmid conjugative DNA transfer: the TraI helicase activity is essential for DNA strand transfer. J. Biol. Chem. 276:23722379.
177. Maurin, M.,, and D. Raoult. 1999. Q fever. Clin. Microbiol. Rev. 12:518553.
178. Mimuro, H.,, T. Suzuki,, J. Tanaka,, M. Asahi,, R. Haas,, and C. Sasakawa. 2002. Grb2 is a key mediator of Helicobacter pylori CagA protein activities. Mol. Cell 10:745755.
179. Miyamoto, H.,, S. Yoshida,, H. Taniguchi,, and H. A. Shuman. 2003. Virulence conversion of Legionella pneumophila by conjugal transfer of chromosomal DNA. J. Bacteriol. 185:67126718.
180. Molmeret, M.,, S. D. Zink,, L. Han,, A. Abu-Zant,, R. Asari,, D. M. Bitar,, and K. Y. Abu. 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.
181. Moncalián, G.,, E. Cabezón,, I. Alkorta,, M. Valle,, F. Moro,, J. M. Valpuesta,, F. M. Goñi,, and F. de la Cruz. 1999. Characterization of ATP and DNA binding activities of TrwB, the coupling protein essential in plasmid R388 conjugation. J. Biol. Chem. 274:3611736124.
182. Moore, D.,, C. M. Hamilton,, K. Maneewannakul,, Y. Mintz,, L. S. Frost,, and K. Ippen-Ihler. 1993. The Escherichia coli K-12 F plasmid gene traX is required for acetylation of F pilin. J. Bacteriol. 175:13751383.
183. Motallebi-Veshareh, M.,, D. Balzer,, E. Lanka,, G. Jagura-Burdzy,, and C. M. Thomas. 1992. Conjugative transfer functions of broad-host-range plasmid RK2 are coregulated with vegetative replication. Mol. Microbiol. 6:907920.
184. Mushegian, A. R.,, K. J. Fullner,, E. V. Koonin,, and E. W. Nester. 1996. A family of lysozyme-like virulence factors in bacterial pathogens of plants and animals. Proc. Natl. Acad. Sci. USA 93:73217326.
185. Müller, A.,, J. Hacker,, and B. C. Brand. 1996. Evidence for apoptosis of human macrophage-like HL-60 cells by Legionella pneumophila infection. Infect. Immun. 64:49004906.
186. 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..
187. Nagai, H.,, and C. R. Roy. 2001. The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO J. 20:59625970.
188. 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.
189. Novak, K. F.,, B. Dougherty,, and M. Peláez. 2001. Actinobacillus actinomycetemcomitans harbours type IV secretion system genes on a plasmid and in the chromosome. Microbiology 147:30273035.
190. Oberhelman, R. A.,, and D. N. Taylor,. 2000. Campylobacter infections in developing countries, p. 139153. In I. Nachamkin, and M. J. Blaser (ed.), Campylobacter, 2nd ed. ASM Press, Washington, D.C.
191. 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 tumefaciensVirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol. Microbiol. 33:12101220.
192. Odenbreit, S.,, J. Püls,, 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.
193. Ogata, H.,, S. Audic,, P. Renesto-Audiffren,, P. E. Fournier,, V. Barbe,, D. Samson,, V. Roux,, P. Cossart,, J. Weissenbach,, J. M. Claverie,, and D. Raoult. 2001. Mechanisms of evolution in Rickettsia conorii and R. prowazekii. Science 293:20932098.
194. 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.
195. 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.
196. Panicker, M. M.,, and E. G. Minkley, Jr. 1992. Purification and properties of the F sex factor TraD protein, an inner membrane conjugal transfer protein. J. Biol. Chem. 267:1276112766.
197. Pansegrau, W.,, G. Ziegelin,, and E. Lanka. 1990a. Covalent association of the traI gene product of plasmid RP4 with the 5'-terminal nucleotide at the relaxation nick site. J. Biol. Chem. 265:1063710644.
198. Pansegrau, W.,, D. Balzer,, V. Kruft,, R. Lurz,, and E. Lanka. 1990b. In vitro assembly of relaxosomes at the transfer origin of plasmid RP4. Proc. Natl. Acad. Sci. USA 87:65556559.
199. Pansegrau, W.,, and E. Lanka. 1996a. Mechanisms of initiation and termination reactions in conjugative DNA processing. Independence of tight substrate binding and catalytic activity of relaxase (TraI) of IncPα plasmid RP4. J. Biol. Chem. 271:1306813076.
200. Pansegrau, W.,, and E. Lanka. 1996b. Enzymology of DNA transfer by conjugative mechanisms. Prog. Nucleic Acid Res. Mol. Biol. 54:197251.
201. Pansegrau, W.,, F. Schoumacher,, B. Hohn,, and E. Lanka. 1993. Site-specific cleavage and joining of singlestranded- DNA by VirD2 protein of Agrobacterium tumefaciens Ti plasmids: analogy to bacterial conjugation. Proc. Natl. Acad. Sci. USA 90:1153811542.
202. Parkhill, J.,, B. W. Wren,, K. Mungall,, J. M. Ketley,, C. Churcher,, D. Basham,, T. Chillingworth,, R. M. Davies,, T. Feltwell,, S. Holroyd,, K. Jagels,, A. V. Karlyshev,, S. Moule,, M. J. Pallen,, C. W. Penn,, M. A. Quail,, M. A. Rajandream,, K. M. Rutherford,, A. H. van Vliet,, S. Whitehead,, and B. G. Barrell. 2000. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403:665668.
203. Patel, S.,, and M. Latterich. 1998. The AAA team: related ATPases with diverse functions. Trends Cell Biol. 8:6571.
204. Patel, S. S.,, and K. M. Picha. 2000. Structure and function of hexameric helicases. Annu. Rev. Biochem. 69:651697.
205. Piers, K. L.,, J. D. Heath,, X. Liang,, K. M. Stephens,, and E. W. Nester. 1996. Agrobacterium tumefaciensmediated transformation of yeast. Proc. Natl. Acad. Sci. USA 93:16131618.
206. Planet, P. J.,, S. C. Kachlany,, R. DeSalle,, D. H. Figurski. 2001. Phylogeny of genes for secretion NTPases: identification of the widespread tadA subfamily and development of a diagnostic key for gene classification. Proc. Natl. Acad. Sci. USA 98:25032508.
207. Purcell, M.,, and H. A. Shuman. 1998. The Legionella pneumophila icmGCDJBF genes are required for killing of human macrophages. Infect. Immun. 66:22452255.
208. Püls, J.,, W. Fischer,, and R. Haas. 2002. Activation of Helicobacter pylori CagA by tyrosine phosphorylation is essential for dephosphorylation of host cell proteins in gastric epithelial cells. Mol. Microbiol. 43:961969.
209. Rabel, C.,, A. M. Grahn,, R. Lurz,, and E. Lanka. 2003. The VirB4 family of proposed traffic nucleoside triphosphatases: common motifs in plasmid RP4 TrbE are essential for conjugation and phage adsorption. J. Bacteriol. 185:10451058.
210. Rain, J. C.,, L. Selig,, H. De Reuse,, V. Battaglia,, C. Reverdy,, S. Simon,, G. Lenzen,, F. Petel,, J. Wojcik,, V. Schächter,, Y. Chemama,, A. Labigne,, and P. Legrain. 2001. The protein-protein interaction map of Helicobacter pylori. Nature 409:211215.
211. Rambow-Larsen, A. A.,, and A. A. Weiss. 2002. The PtlE protein of Bordetella pertussis has peptidoglycanase activity required for Ptl-mediated pertussis toxin secretion. J. Bacteriol. 184:28632869.
212. Ranson, N. A.,, G. W. Farr,, A. M. Roseman,, B. Gowen,, W. A. Fenton,, A. L. Horwich,, and H. R. Saibil. 2001. ATP-bound states of GroEL captured by cryo-electron microscopy. Cell 107:869879.
213. Rice, S.,, A. W. Lin,, D. Safer,, C. L. Hart,, N. Naber,, B. O. Carragher,, S. M. Cain,, E. Pechatnikova,, E. M. Wilson-Kubalek,, M. Whittaker,, E. Pate,, R. Cooke,, E. W. Taylor,, R. A. Milligan,, and R. D. Vale. 1999. A structural change in the kinesin motor protein that drives motility. Nature 402:778784.
214. Ridenour, D. A.,, S. L. Cirillo,, S. Feng,, M. M. Samrakandi,, and J. D. Cirillo. 2003. Identification of a gene that affects the efficiency of host cell infection by Legionella pneumophila in a temperature-dependent fashion. Infect. Immun. 71:62566263.
215. Rivas, S.,, S. Bolland,, E. Cabezón,, F. M. Goñi,, and F. de la Cruz. 1997. TrwD, a protein encoded by the IncW plasmid R388, displays an ATP hydrolase activity essential for bacterial conjugation. J. Biol. Chem. 272:2558325590.
216. Rohde, M.,, J. Püls,, R. Buhrdorf,, W. Fischer,, and R. Haas. 2003. A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system. Mol. Microbiol. 49:219234.
217. Rossi, L.,, B. Tinland,, and B. Hohn,. 1998. Role of virulence proteins of Agrobacterium in the plant, p. 303320. In H. P. Spaink,, A. Kondorosi,, and P. J. J. Hooykaas (ed.), The Rhizobiaceae:Molecular Biology of Model Plant-Associated Bacteria. Kluwer Academic Publishers, Dordrecht, The Netherlands.
218. Rouiller, I.,, V. M. Butel,, M. Latterich,, R. A. Milligan,, and E. M. Wilson-Kubalek. 2000. A major conformational change in p97 AAA ATPase upon ATP binding. Mol. Cell 6:14851490.
219. Roy, C. R.,, and L. G. Tilney. 2002. The road less traveled: transport of Legionella to the endoplasmic reticulum. J. Cell Biol. 158:415419.
220. Sagulenko, V.,, E. Sagulenko,, S. Jakubowski,, E. Spudich,, and P. J. Christie. 2001a. VirB7 lipoprotein is exocellular and associates with the Agrobacterium tumefaciens T pilus. J. Bacteriol. 183:36423651.
221. Sagulenko, E.,, V. Sagulenko,, J. Chen,, and P. J. Christie. 2001b. Role of Agrobacterium VirB11 ATPase in T-pilus assembly and substrate selection. J. Bacteriol. 183:58135825.
222. Salanoubat, M.,, S. Genin,, F. Artiguenave,, J. Gouzy,, S. Mangenot,, M. Arlat,, A. Billault,, P. Brottier,, J. C. Camus,, L. Cattolico,, M. Chandler,, N. Choisne,, C. Claudel-Renard,, S. Cunnac,, N. Demange,, C. Gaspin,, M. Lavie,, A. Moisan,, C. Robert,, W. Saurin,, T. Schiex,, P. Siguier,, P. Thébault,, M. Whalen,, P. Wincker,, M. Levy,, J. Weissenbach,, and C. A. Boucher. 2002. Genome sequence of the plant pathogen Ralstonia solanacearum. Nature 415:497502.
223. Salmond, G. P. C. 1994. Secretion of extracellular virulence factors by plant pathogenic bacteria. Annu. Rev. Phytopathol. 32:181200.
224. Samartino, L. E.,, and F. M. Enright. 1993. Pathogenesis of abortion of bovine brucellosis. Comp. Immunol. Microbiol. Infect. Dis. 16:95101.
225. Savvides, S. N.,, H. J. Yeo,, M. R. Beck,, F. Blaesing,, R. Lurz,, E. Lanka,, R. Buhrdorf,, W. Fischer,, R. Haas,, and G. Waksman. 2003. VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 22:19691980.
226. 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.
227. Schmidt-Eisenlohr, H.,, N. Domke,, C. Angerer,, G. Wanner,, P. C. Zambryski,, and C. Baron. 1999a. Vir proteins stabilize VirB5 and mediate its association with the T pilus of Agrobacterium tumefaciens. J. Bacteriol. 181:74857492.
228. Schmidt-Eisenlohr, H.,, N. Domke,, and C. Baron. 1999b. TraC of IncN plasmid pKM101 associates with membranes and extracellular high-molecular-weight structures in Escherichia coli. J. Bacteriol. 181:55635571.
229. Schneider, E.,, and S. Hunke. 1998. ATP-binding-cassette (ABC) transport systems: functional and structural aspects of the ATP-hydrolyzing subunits/domains. FEMS Microbiol. Rev. 22:120.
230. Schneiker, S.,, M. Keller,, M. Dröge,, E. Lanka,, A. Pühler,, and W. Selbitschka. 2001. The genetic organization and evolution of the broad host range mercury resistance plasmid pSB102 isolated from a microbial population residing in the rhizosphere of alfalfa. Nucleic Acids Res. 29:51695181.
231. Schrammeijer, B.,, A. Den Dulk-Ras,, A. C. Vergunst,, E. Jurado Jacome,, and P. J. J. Hooykaas. 2003. Analysis of Vir protein translocation from Agrobacterium tumefaciens using Saccharomyces cerevisiae as a model: evidence for transport of a novel effector protein VirE3. Nucleic Acids Res. 31:860868.
232. Schröder, G.,, S. Krause,, E. L. Zechner,, B. Traxler,, H. J. Yeo,, R. Lurz,, G. Waksman,, and E. Lanka. 2002. TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV secretion system: inner membrane gate for exported substrates? J. Bacteriol. 184:27672779.
233. Schröder, G.,, and E. Lanka. 2003. TraG-like proteins of type IV secretion systems: functional dissection of the multiple activities of TraG (RP4) and TrwB (R388). J. Bacteriol. 185:43714381.
234. 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.
235. Schulein, R.,, P. Guye,, T. A. Rhomberg,, M. C. Schmid,, G. Schröder,, 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.
236. Segal, E. D.,, J. Cha,, J. Lo,, S. Falkow,, and L. S. Tompkins. 1999a. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. USA 96:1455914564.
237. 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.
238. Segal, G.,, J. J. Russo,, and H. A. Shuman. 1999b. Relationships between a new type IV secretion system and the icm/dot virulence system of Legionella pneumophila. Mol. Microbiol. 34:799809.
239. Segal, G.,, and H. A. Shuman. 1997. Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect.Immun. 65:50575066.
240. Selbach, M.,, S. Moese,, T. F. Meyer,, and S. Backert. 2002. Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms. Infect. Immun. 70:665671.
241. Selmi, C.,, D. L. Balkwill,, P. Invernizzi,, A. A. Ansari,, R. L. Coppel,, M. Podda,, P. S. Leung,, T. P. Kenny,, J. Van De Water,, M. H. Nantz,, M. J. Kurth,, and M. E. Gershwin. 2003. Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium. Hepatology 38:12501257.
242. Seubert, A.,, R. Hiestand,, F. de la Cruz,, and C.