Chapter 9 : Type III Secretion Machinery and Effectors

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The translocated effectors harbor many different activities and can be used in different combinations by various bacteria to exert highly specific and unique effects on the host cell. Additionally, even homologous effectors with identical enzymatic activity can vary enough in substrate specificity and delivery to make their effect on the host cell tailored for a given pathogen. In understanding the biology of these systems, moderate- and high-resolution structural information has often played a key role and, furthermore, revealed aspects and themes in the pathogenesis of these systems that were much less clear from data generated from more indirect experimental techniques. This chapter represents only a skimming of the surface in examining these systems from a structural point of view, but it is nonetheless informative. Composed of more than 20 proteins and related to the flagellar assembly apparatus, type III secretion systems are one of the most complex protein secretion systems to be discovered. Rather than presenting the structures based on their fold or biochemical activity or on the species which utilize them, the chapter is organized in biological themes and examines the structures in related functional contexts. Detailed structural analyses of type III secretion virulence systems are only in their infancy. The field awaits high-resolution work on the needle complex, the translocon, the bacterial side elements, and the remaining arsenal of effector molecules used by the different gram-negative pathogens utilizing this translocation system in plants and animals.

Citation: Stebbins C. 2005. Type III Secretion Machinery and Effectors, p 149-177. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch9

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Type III Secretion System
Bacterial Proteins
Type III Secretion System Proteins
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Image of Figure 1.
Figure 1.

The type III secretion system needle complex. (A) An electron micrograph of osmotically shocked bacterial cells from serovar Typhimurium reveals a structure with an inner membrane-associated base (white arrow), outer membrane ring, and filamentous extension (the “needle”; black arrow). Reprinted from with permission. (B) Higher-resolution EM reconstructions of isolated needle complexes from reveal the details of the substructures of the secretion apparatus. The needle filament (light gray arrow), the outer membrane secretin rings (white arrow), the periplasmic rings (dark gray arrow), and the inner membrane rings (black arrow) are shown. Reprinted from with permission. (C) Schematic of the needle complex, illustrating the docking of the filament with the host cell pore, the inner and outer membrane elements such as the secretin rings, periplasmic rings, and inner membrane rings. The bacterial cytoplasm contains homodimeric secretion chaperones binding to effector molecules prior to translocation through the needle complex.

Citation: Stebbins C. 2005. Type III Secretion Machinery and Effectors, p 149-177. In Waksman G, Caparon M, Hultgren S (ed), Structural Biology of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818395.ch9
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1. Abe, A.,, M. de Grado,, R. A. Pfuetzner,, C. Sanchez-Sanmartin,, R. Devinney,, J. L. Puente,, N. C. Strynadka,, and B. B. Finlay. 1999. Enteropathogenic Escherichia coli translocated intimin receptor, Tir, requires a specific chaperone for stable secretion. Mol. Microbiol. 33:11621175.
2. Aktories, K.,, G. Schmidt,, and I. Just. 2000. Rho GTPases as targets of bacterial protein toxins. Biol. Chem. 381:421426.
3. Bakshi, C. S.,, V. P. Singh,, M. W. Wood,, P. W. Jones,, T. S. Wallis,, and E. E. Galyov. 2000. Identification of SopE2, a Salmonella secreted protein which is highly homologous to SopE and involved in bacterial invasion of epithelial cells. J. Bacteriol. 182:23412344.
4. Barbieri, J. T.,, M. J. Riese,, and K. Aktories. 2002. Bacterial toxins that modify the actin cytoskeleton. Annu. Rev. Cell Dev. Biol. 18:315344.
5. Barford, D.,, A. J. Flint,, and N. K. Tonks. 1994. Crystal structure of human protein tyrosine phosphatase 1B. Science 263:13971404.
6. Barford, D.,, Z. Jia,, and N. K. Tonks. 1995. Protein tyrosine phosphatases take off. Nat. Struct. Biol. 2:10431053.
7. Birtalan, S.,, and P. Ghosh. 2001. Structure of the Yersinia type III secretory system chaperone SycE. Nat. Struct. Biol. 8:974978.
8. Birtalan, S. C.,, R. M. Phillips,, and P. Ghosh. 2002. Three-dimensional secretion signals in chaperone-effector complexes of bacterial pathogens. Mol. Cell 9:971980.
9. Black, D. S.,, and J. B. Bliska. 1997. Identification of p130Cas as a substrate of YersiniaYopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. EMBO J. 16:27302744.
10. Black, D. S.,, and J. B. Bliska. 2000. The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence. Mol. Microbiol. 37:515527.
11. Bliska, J. B. 1995. Crystal structure of the Yersinia tyrosine phosphatase. Trends Microbiol. 3:125127.
12. Bliska, J. B.,, K. L. Guan,, J. E. Dixon,, and S. Falkow. 1991. Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc. Natl. Acad. Sci. USA 88:11871191.
13. Blocker, A.,, P. Gounon,, E. Larquet,, K. Niebuhr,, V. Cabiaux,, C. Parsot,, and P. Sansonetti. 1999. The tripartite type III secreton of Shigella flexneri inserts IpaB and IpaC into host membranes. J. Cell Biol. 147:683693.
14. Blocker, A.,, N. Jouihri,, E. Larquet,, P. Gounon,, F. Ebel,, C. Parsot,, P. Sansonetti,, and A. Allaoui. 2001. Structure and composition of the Shigella flexneri “needle complex,” a part of its type III secreton. Mol. Microbiol. 39:652663.
15. Boland, A.,, M. P. Sory,, M. Iriarte,, C. Kerbourch,, P. Wattiau,, and G. R. Cornelis. 1996. Status of YopM and YopN in the Yersinia Yop virulon: YopM of Y. enterocolitica is internalized inside the cytosol of PU5-1.8nmacrophages by the YopB, D, N delivery apparatus. EMBO J. 15:51915201.
16. Bourne, H. R.,, D. A. Sanders,, and F. McCormick. 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125132.
17. Bronstein, P. A.,, E. A. Miao,, and S. I. Miller. 2000. InvB is a type III secretion chaperone specific for SspA. J. Bacteriol. 182:66386644.
18. Brown, I. R.,, J. W. Mansfield,, S. Taira,, E. Roine,, and M. Romantschuk. 2001. Immunocytochemical localization of HrpA and HrpZ supports a role for the Hrp pilus in the transfer of effector proteins from Pseudomonas syringae pv. tomato across the host plant cell wall. Mol. Plant-Microbe Interact. 14:394404.
19. Buchwald, G.,, A. Friebel,, J. E. Galan,, W. D. Hardt,, A. Wittinghofer,, and K. Scheffzek. 2002. Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J. 21:32863295.
20. Burghout, P.,, R. Van Boxtel,, P. Van Gelder,, P. Ringler,, S. A. Muller,, J. Tommassen,, M. Koster. 2004. Structure and electrophysiological properties of the YscC secretin from the type III secretion system of Yersinia enterocolitica. J. Bacteriol. 186:46454654.
21. Buttner, D.,, and U. Bonas. 2002a. Getting across—bacterial type III effector proteins on their way to the plant cell. EMBO J. 21:53135322.
22. Buttner, D.,, and U. Bonas. 2002b. Port of entry—the type III secretion translocon. Trends Microbiol. 10:186192.
23. Buttner, D.,, D. Nennstiel,, B. Klusener,, and U. Bonas. 2002. Functional analysis of HrpF, a putative type III translocon protein from Xanthomonas campestris pv. vesicatoria. J. Bacteriol. 184:23892398.
24. Cherfils, J.,, and P. Chardin. 1999. GEFs: structural basis for their activation of small GTP-binding proteins. Trends Biochem. Sci. 24:306311.
25. Cohen, M. L. 1992. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257: 10501055.
26. Cohen, M. L. 1994. Antimicrobial resistance: prognosis for public health. Trends Microbiol. 2:422425.
27. Cohen, M. L. 2000. Changing patterns of infectious disease. Nature 406:762767.
28. Collier-Hyams, L. S.,, H. Zeng,, J. Sun,, A. D. Tomlinson,, Z. Q. Bao,, H. Chen,, J. L. Madara,, K. Orth,, and A. S. Neish. 2002. Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-kappa B pathway. J. Immunol. 169:28462850.
29. Cordes, F. S.,, K. Komoriya,, E. Larquet,, S. Yang,, E. H. Egelman,, A. Blocker,, and S. M. Lea. 2003. Helical structure of the needle of the type III secretion system of Shigella flexneri. J. Biol. Chem. 278:1710317107.
30. Cornelis, G. R. 2002. The Yersinia Ysc-Yop virulence apparatus. Int. J. Med. Microbiol. 291:455462.
31. Cornelis, G. R.,, and F. Van Gijsegem. 2000. Assembly and function of type III secretory systems. Annu. Rev. Microbiol. 54:735774.
32. Crago, A. M.,, and V. Koronakis. 1998. Salmonella InvG forms a ring-like multimer that requires the InvH lipoprotein for outer membrane localization. Mol. Microbiol. 30:4756.
33. Daniell, S. J.,, E. Kocsis,, E. Morris,, S. Knutton,, F. P. Booy,, and G. Frankel. 2003. 3D structure of EspA filaments from enteropathogenic Escherichia coli. Mol. Microbiol. 49:301308.
34. Daniell, S. J.,, N. Takahashi,, R. Wilson,, D. Friedberg,, I. Rosenshine,, F. P. Booy,, R. K. Shaw,, S. Knutton,, G. Frankel,, and S. Aizawa. 2001. The filamentous type III secretion translocon of enteropathogenic Escherichia coli. Cell Microbiol. 3:865871.
35. Darwin, K. H.,, L. S. Robinson,, and V. L. Miller. 2001. SigE is a chaperone for the Salmonella enterica serovar Typhimurium invasion protein SigD. J. Bacteriol. 183:14521454.
36. Dixon, J. E. 1995. Structure and catalytic properties of protein tyrosine phosphatases. Ann. N.Y. Acad. Sci. 766: 1822.
37. Elliott, S. J.,, S. W. Hutcheson,, M. S. Dubois,, J. L. Mellies,, L. A. Wainwright,, M. Batchelor,, G. Frankel,, S. Knutton,, and J. B. Kaper. 1999. Identification of CesT, a chaperone for the type III secretion of Tir in enteropathogenic Escherichia coli. Mol. Microbiol. 33:11761189.
38. Evdokimov, A. G.,, D. E. Anderson,, K. M. Routzahn,, and D. S. Waugh. 2001a. Unusual molecular architecture of the Yersinia pestis cytotoxin YopM: a leucine-rich repeat protein with the shortest repeating unit. J. Mol. Biol. 312:807821.
39. Evdokimov, A. G.,, J. E. Tropea,, K. M. Routzahn,, T. D. Copeland,, and D. S. Waugh. 2001b. Structure of the N-terminal domain of Yersinia pestisYopH at 2.0 Å resolution. Acta Crystallogr. Ser. D 57:793799.
40. Evdokimov, A. G.,, J. E. Tropea,, K. M. Routzahn,, and D. S. Waugh. 2002a. Crystal structure of the Yersinia pestis GTPase activator YopE. Protein Sci. 11:401408.
41. Evdokimov, A. G.,, J. E. Tropea,, K. M. Routzahn,, and D. S. Waugh. 2002b. Three-dimensional structure of the type III secretion chaperone SycE from Yersinia pestis. Acta Crystallogr. Ser. D 58:398406.
42. Fauman, E. B.,, and M. A. Saper. 1996. Structure and function of the protein tyrosine phosphatases. Trends Biochem. Sci. 21:413417.
43. Fauman, E. B.,, C. Yuvaniyama,, H. L. Schubert,, J. A. Stuckey,, and M. A. Saper. 1996. The X-ray crystal structures of Yersinia tyrosine phosphatase with bound tungstate and nitrate. Mechanistic implications. J. Biol. Chem. 271:1878018788.
44. Fraser, C. M.,, and M. R. Dando. 2001. Genomics and future biological weapons: the need for preventive action by the biomedical community. Nat. Genet. 29:253256.
45. Fu, Y.,, and J. E. Galan. 1998. Identification of a specific chaperone for SptP, a substrate of the centisome 63 type III secretion system of Salmonella typhimurium. J. Bacteriol. 180:33933399.
46. Fu, Y.,, and J. E. Galan. 1999. A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401:293297.
47. Galan, J. E. 2001. Salmonella interactions with host cells: type III secretion at work. Annu. Rev. Cell Dev. Biol. 17:5386.
48. Galan, J. E.,, and A. Collmer. 1999. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284:13221328.
49. Galan, J. E.,, and D. Zhou. 2000. Striking a balance: modulation of the actin cytoskeleton by Salmonella. Proc. Natl. Acad. Sci. USA 97:87548761.
50. Galyov, E. E.,, S. Hakansson,, A. Forsberg,, and H. Wolf-Watz. 1993. A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. Nature 361:730732.
51. Gamblin, S. J.,, and S. J. Smerdon. 1998. GTPase-activating proteins and their complexes. Curr. Opin. Struct. Biol. 8:195201.
52. Geiser, T. K.,, B. I. Kazmierczak,, L. K. Garrity-Ryan,, M. A. Matthay,, and J. N. Engel. 2001. Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. Cell. Microbiol. 3:223236.
53. Ginocchio, C. C.,, S. B. Olmsted,, C. L. Wells,, and J. E. Galan. 1994. Contact with epithelial cells induces the formation of surface appendages on Salmonella typhimurium. Cell 76:717724.
54. Goehring, U. M.,, G. Schmidt,, K. J. Pederson,, K. Aktories,, and J. T. Barbieri. 1999. The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J. Biol. Chem. 274:3636936372.
55. Grosdent, N.,, I. Maridonneau-Parini,, M. P. Sory,, and G. R. Cornelis. 2002. Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect. Immun. 70:41654176.
56. Guan, K. L.,, and J. E. Dixon. 1990. Protein tyrosine phosphatase activity of an essential virulence determinant in Yersinia. Science 249:553556.
57. Guan, K. L.,, and J. E. Dixon. 1993. Bacterial and viral protein tyrosine phosphatases. Semin. Cell Biol. 4:389 396.
58. Hakansson, S.,, E. E. Galyov,, R. Rosqvist,, and H. Wolf-Watz. 1996a. The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol. Microbiol. 20:593603.
59. Hakansson, S.,, K. Schesser,, C. Persson,, E. E. Galyov,, R. Rosqvist,, F. Homble,, and H. Wolf-Watz. 1996b. The YopB protein of Yersinia pseudotuberculosis is essential for the translocation of Yop effector proteins across the target cell plasma membrane and displays a contact-dependent membrane disrupting activity. EMBO J. 15:58125823.
60. Hall, A. 1998. Rho GTPases and the actin cytoskeleton. Science 279:509514.
61. Hamburger, Z. A.,, M. S. Brown,, R. R. Isberg,, and P. J. Bjorkman. 1999. Crystal structure of invasin: a bacterial integrin-binding protein. Science 286:291295.
62. Hamid, N.,, A. Gustavsson,, K. Andersson,, K. McGee,, C. Persson,, C. E. Rudd,, and M. Fallman. 1999. YopH dephosphorylates Cas and Fyn-binding protein in macrophages. Microb. Pathog. 27:231242.
63. Han, S.,, A. S. Arvai,, S. B. Clancy,, and J. A. Tainer. 2001. Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis. J. Mol. Biol. 305:95107.
64. Han, S.,, J. A. Craig,, C. D. Putnam,, N. B. Carozzi,, and J. A. Tainer. 1999. Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex. Nat. Struct. Biol. 6:932936.
65. Hardt, W. D.,, L. M. Chen,, K. E. Schuebel,, X. R. Bustelo,, and J. E. Galan. 1998a. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93:815 826.
66. Hardt, W. D.,, H. Urlaub,, and J. E. Galan. 1998b. A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc. Natl. Acad. Sci. USA 95:25742579.
67. Hartl, F. U.,, and M. Hayer-Hartl. 2002. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:18521858.
68. Hayward, R. D.,, and V. Koronakis. 1999. Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella. EMBO J. 18:49264934..
69. Hayward, R. D.,, and V. Koronakis. 2002. Direct modulation of the host cell cytoskeleton by Salmonella actinbinding proteins. Trends Cell Biol. 12:1520.
70. Hayward, R. D.,, E. J. McGhie,, and V. Koronakis. 2000. Membrane fusion activity of purified SipB, a Salmonella surface protein essential for mammalian cell invasion. Mol. Microbiol. 37:727739.
71. He, S. Y.,, and Q. Jin. 2003. The Hrp pilus: learning from flagella. Curr. Opin. Microbiol. 6:1519.
72. Higashide, W.,, S. Dai,, V. P. Hombs,, and D. Zhou. 2002. Involvement of SipA in modulating actin dynamics during Salmonella invasion into cultured epithelial cells. Cell. Microbiol. 4:357365.
73. Hirshberg, M.,, R. W. Stockley,, G. Dodson,, and M. R. Webb. 1997. The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat. Struct. Biol. 4:147152.
74. Hoiczyk, E.,, and G. Blobel. 2001. Polymerization of a single protein of the pathogen Yersinia enterocolitica into needles punctures eukaryotic cells. Proc. Natl. Acad. Sci. USA 98:46694674.
75. Holm, L.,, and C. Sander. 1993. Protein structure comparison by alignment of distance matrices. J. Mol. Biol. 233:123138.
76. Hu, W.,, J. Yuan,, Q. L. Jin,, P. Hart,, and S. Y. He. 2001. Immunogold labeling of Hrp pili of Pseudomonas syringae pv. tomato assembled in minimal medium and in planta. Mol. Plant-Microbe Interact. 14:234 241.
77. Hueck, C. J. 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62:379433.
78. Ihara, K.,, S. Muraguchi,, M. Kato,, T. Shimizu,, M. Shirakawa,, S. Kuroda,, K. Kaibuchi,, and T. Hakoshima. 1998. Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue. J. Biol. Chem. 273:96569666.
79. Iriarte, M.,, and G. R. Cornelis. 1998. YopT, a new YersiniaYop effector protein, affects the cytoskeleton of host cells. Mol. Microbiol. 29:915929.
80. Isberg, R. R.,, and J. M. Leong. 1988. Cultured mammalian cells attach to the invasin protein of Yersinia pseudotuberculosis. Proc. Natl. Acad. Sci. USA 85:66826686.
81. Isberg, R. R.,, D. L. Voorhis,, and S. Falkow. 1987. Identification of invasin: a protein that allows enteric bacteria to penetrate cultured mammalian cells. Cell 50:769778.
82. Jepson, M. A.,, B. Kenny,, and A. D. Leard. 2001. Role of sipA in the early stages of Salmonella typhimurium entry into epithelial cells. Cell. Microbiol. 3:417426.
83. Jia, Z.,, D. Barford,, A. J. Flint,, and N. K. Tonks. 1995. Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B. Science 268:17541758.
84. Jin, Q.,, and S. Y. He. 2001. Role of the Hrp pilus in type III protein secretion in Pseudomonas syringae. Science 294:25562558.
85. Jin, Q.,, W. Hu,, I. Brown,, G. McGhee,, P. Hart,, A. L. Jones,, and S. Y. He. 2001. Visualization of secreted Hrp and Avr proteins along the Hrp pilus during type III secretion in Erwinia amylovora and Pseudomonas syringae. Mol. Microbiol. 40:11291139.
86. Journet, L.,, C. Agrain,, P. Broz,, and G. R. Cornelis. 2003. The needle length of bacterial injectisomes is determined by a molecular ruler. Science 302:17571760.
87. Kaniga, K.,, J. Uralil,, J. B. Bliska,, and J. E. Galan. 1996. A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium. Mol. Microbiol. 21:633641.
88. Khandelwal, P.,, K. Keliikuli,, C. L. Smith,, M. A. Saper,, and E. R. Zuiderweg. 2002. Solution structure and phosphopeptide binding to the N-terminal domain of YersiniaYopH: comparison with a crystal structure. Biochemistry 41:1142511437.
89. Kimbrough, T. G.,, and S. I. Miller. 2000. Contribution of Salmonella typhimurium type III secretion components to needle complex formation. Proc. Natl. Acad. Sci. USA 97:1100811013.
90. Kimbrough, T. G.,, and S. I. Miller. 2002. Assembly of the type III secretion needle complex of Salmonella typhimurium. Microbes Infect. 4:7582.
91. Knutton, S.,, I. Rosenshine,, M. J. Pallen,, I. Nisan,, B. C. Neves,, C. Bain,, C. Wolff,, G. Dougan,, and G. Frankel. 1998. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J. 17:21662176.
92. Kobe, B.,, and A. V. Kajava. 2001. The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol. 11:725732.
93. Kubori, T.,, Y. Matsushima,, D. Nakamura,, J. Uralil,, M. Lara-Tejero,, A. Sukhan,, J. E. Galan,, and S. I. Aizawa. 1998. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280:602605.
94. Kubori, T.,, A. Sukhan,, S. I. Aizawa,, and J. E. Galan. 2000. Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system. Proc. Natl. Acad. Sci. USA 97:1022510230.
95. Kubori, T.,, and J. E. Galan. 2003. Temporal regulation of salmonella virulence effector function by proteasome- dependent protein degradation. Cell 115:333342.
96. Leong, J. M.,, R. S. Fournier,, and R. R. Isberg. 1991. Mapping and topographic localization of epitopes of the Yersinia pseudotuberculosis invasin protein. Infect. Immun. 59:34243433.
97. Lerm, M.,, G. Schmidt,, and K. Aktories. 2000. Bacterial protein toxins targeting rho GTPases. FEMS Microbiol. Lett. 188:16.
98. Lesnick, M. L.,, N. E. Reiner,, J. Fierer,, and D. G. Guiney. 2001. The Salmonella spvB virulence gene encodes an enzyme that ADP-ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells. Mol. Microbiol. 39:14641470.
99. Leung, K. Y.,, and S. C. Straley. 1989. The yopM gene of Yersinia pestis encodes a released protein having homology with the human platelet surface protein GPIb alpha. J. Bacteriol. 171:46234632.
100. Lilic, M.,, V. E. Galkin,, A. Orlova,, M. S. VanLoock,, E. H. Egelman,, and C. E. Stebbins. 2003. Salmonella SipA polymerizes actin by stapling filaments with nonglobular protein arms. Science 301:19181921.
101. Luo, Y.,, M. G. Bertero,, E. A. Frey,, R. A. Pfuetzner,, M. R. Wenk,, L. Creagh,, S. L. Marcus,, D. Lim,, F. Sicheri,, C. Kay,, C. Haynes,, B. B. Finlay,, and N. C. Strynadka. 2001. Structural and biochemical characterization of the type III secretion chaperones CesT and SigE. Nat. Struct. Biol. 8:10311036.
102. Marcus, S. L.,, M. R. Wenk,, O. Steele-Mortimer,, and B. B. Finlay. 2001. A synaptojanin-homologous region of Salmonella typhimurium SigD is essential for inositol phosphatase activity and Akt activation. FEBS Lett. 494:201207.
103. McDonald, C.,, P. O. Vacratsis,, J. B. Bliska,, and J. E. Dixon. 2003. The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J. Biol. Chem. 278:1851418523.
104. McGhie, E. J.,, R. D. Hayward,, and V. Koronakis. 2001. Cooperation between actin-binding proteins of invasive Salmonella: SipA potentiates SipC nucleation and bundling of actin. EMBO J. 20:21312139.
105. Meijer, L. K.,, K. Schesser,, H. Wolf-Watz,, P. Sassone-Corsi,, and S. Pettersson. 2000. The bacterial protein YopJ abrogates multiple signal transduction pathways that converge on the transcription factor CREB. Cell. Microbiol. 2:231238.
106. Monack, D. M.,, J. Mecsas,, N. Ghori,, and S. Falkow. 1997. Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc. Natl. Acad. Sci. USA 94:1038510390.
107. Montagna, L. G.,, M. I. Ivanov,, and J. B. Bliska. 2001. Identification of residues in the N-terminal domain of the Yersinia tyrosine phosphatase that are critical for substrate recognition. J. Biol. Chem. 276:50055011.
108. Murli, S.,, R. O. Watson,, and J. E. Galan. 2001. Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells. Cell. Microbiol. 3:795810.
109. Nassar, N.,, G. R. Hoffman,, D. Manor,, J. C. Clardy,, and R. A. Cerione. 1998. Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP. Nat. Struct. Biol. 5:10471052.
110. Neves, B. C.,, S. Knutton,, L. R. Trabulsi,, V. Sperandio,, J. B. Kaper,, G. Dougan,, and G. Frankel. 1998. Molecular and ultrastructural characterisation of EspA from different enteropathogenic Escherichia coli serotypes. FEMS Microbiol. Lett. 169:7380.
111. Neyt, C.,, and G. R. Cornelis. 1999. Insertion of a Yop translocation pore into the macrophage plasma membrane by Yersinia enterocolitica: requirement for translocators YopB and YopD, but not LcrG. Mol. Microbiol. 33:971981.
112. Nixdorff, K.,, J. Brauburger,, and D. Hahlbohm. 2000. The biotechnology revolution: the science and applications. NATO ASI Ser. 32:77124.
113. Norris, F. A.,, M. P. Wilson,, T. S. Wallis,, E. E. Galyov,, and P. W. Majerus. 1998. SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc. Natl. Acad. Sci. USA 95:14057 14059.
114. Opalka, N.,, R. Beckmann,, N. Boisset,, M. N. Simon,, M. Russel,, S. A. Darst. 2003. Structure of the filamentous phage pIV multimer by cryo-electron microscopy. J. Mol. Biol. 325:461470.
115. Orth, K.,, Z. Xu,, M. B. Mudgett,, Z. Q. Bao,, L. E. Palmer,, J. B. Bliska,, W. F. Mangel,, B. Staskawicz,, and J. E. Dixon. 2000. Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science 290:15941597.
116. Osiecki, J. C.,, J. Barker,, W. L. Picking,, A. B. Serfis,, E. Berring,, S. Shah,, A. Harrington,, and W. D. Picking. 2001. IpaC from Shigella and SipC from Salmonella possess similar biochemical properties but are functionally distinct. Mol. Microbiol. 42:469481.
117. Page, A. L.,, P. Sansonetti,, and C. Parsot. 2002. Spa15 of Shigella flexneri, a third type of chaperone in the type III secretion pathway. Mol. Microbiol. 43:15331542.
118. Page, A. L.,, and C. Parsot. 2002. Chaperones of the type III secretion pathway: jacks of all trades. Mol. Microbiol. 46:111.
119. Palmer, L. E.,, S. Hobbie,, J. E. Galan,, and J. B. Bliska. 1998. YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-alpha production and downregulation of the MAP kinases p38 and JNK. Mol. Microbiol. 27:953965.
120. Palmer, L. E.,, A. R. Pancetti,, S. Greenberg,, and J. B. Bliska. 1999. YopJ of Yersinia spp. is sufficient to cause downregulation of multiple mitogen-activated protein kinases in eukaryotic cells. Infect. Immun. 67:708716.
121. Pang, T.,, Z. A. Bhutta,, B. B. Finlay,, and M. Altwegg. 1995. Typhoid fever and other salmonellosis: a continuing challenge. Trends Microbiol. 3:253255.
122. Perry, R. D.,, and J. D. Fetherston. 1997. Yersinia pestis—etiologic agent of plague. Clin. Microbiol. Rev. 10: 3566.
123. Persson, C.,, N. Carballeira,, H. Wolf-Watz,, and M. Fallman. 1997. The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. EMBO J. 16:23072318.
124. Rittinger, K.,, P. A. Walker,, J. F. Eccleston,, K. Nurmahomed,, D. Owen,, E. Laue,, S. J. Gamblin,, and S. J. Smerdon. 1997a. Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. Nature 388:693697.
125. Rittinger, K.,, P. A. Walker,, J. F. Eccleston,, S. J. Smerdon,, and S. J. Gamblin. 1997b. Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue. Nature 389:758762.
126. Roine, E.,, W. Wei,, J. Yuan,, E. L. Nurmiaho-Lassila,, N. Kalkkinen,, M. Romantschuk,, and S. Y. He. 1997. Hrp pilus: an hrp-dependent bacterial surface appendage produced by Pseudomonas syringae pv. tomato DC3000. Proc. Natl. Acad. Sci. USA 94:34593464.
127. Rudolph, M. G.,, C. Weise,, S. Mirold,, B. Hillenbrand,, B. Bader,, A. Wittinghofer,, and W. D. Hardt. 1999. Biochemical analysis of SopE from Salmonella typhimurium, a highly efficient guanosine nucleotide exchange factor for RhoGTPases. J. Biol. Chem. 274:3050130509.
128. Samatey, F. A.,, K. Imada,, S. Nagashima,, F. Vonderviszt,, T. Kumasaka,, M. Yamamoto,, and K. Namba. 2001. Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling. Nature 410:331337.
129. Schesser, K.,, A.-K. Spiik,, J.-M. Dukuzumuremyi,, M. F. Neurath,, S. Pettersson,, and H. Wolf-Watz. 1998. The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol. Microbiol. 28: 10671079.
130. Schuch, R.,, and A. T. Maurelli. 2001. MxiM and MxiJ, base elements of the Mxi-Spa type III secretion system of Shigella, interact with and stabilize the MxiD secretin in the cell envelope. J. Bacteriol. 183:69916998.
131. Sekiya, K.,, M. Ohishi,, T. Ogino,, K. Tamano,, C. Sasakawa,, and A. Abe. 2001. Supermolecular structure of the enteropathogenic Escherichia coli type III secretion system and its direct interaction with the EspA-sheath- like structure. Proc. Natl. Acad. Sci. USA 98:1163811643.
132. Shao, F.,, P. M. Merritt,, Z. Bao,, R. W. Innes,, and J. E. Dixon. 2002. A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 109:575588.
133. Skrzypek, E.,, C. Cowan,, and S. C. Straley. 1998. Targeting of the Yersinia pestisYopM protein into HeLa cells and intracellular trafficking to the nucleus. Mol. Microbiol. 30:10511065.
134. Smith, C. L.,, P. Khandelwal,, K. Keliikuli,, E. R. Zuiderweg,, and M. A. Saper. 2001. Structure of the type III secretion and substrate-binding domain of YersiniaYopH phosphatase. Mol. Microbiol. 42:967979.
135. Sory, M. P.,, A. Boland,, I. Lambermont,, and G. R. Cornelis. 1995. Identification of the YopE and YopH domains required for secretion and internalization into the cytosol of macrophages, using the cyaA gene fusion approach. Proc. Natl. Acad. Sci. USA 92:1199812002.
136. Sprang, S. R. 1997. G proteins, effectors and GAPs: structure and mechanism. Curr. Opin. Struct. Biol. 7:849856.
137. Stebbins, C. E.,, and J. E. Galan. 2000. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol. Cell 6:14491460.
138. Stebbins, C. E.,, and J. E. Galan. 2001a. Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion. Nature 414:7781.
139. Stebbins, C. E.,, and J. E. Galan. 2001b. Structural mimicry in bacterial virulence. Nature 412:701705.
140. Steele-Mortimer, O.,, J. H. Brumell,, L. A. Knodler,, S. Meresse,, A. Lopez,, and B. B. Finlay. 2002. The invasion- associated type III secretion system of Salmonella enterica serovar Typhimurium is necessary for intracellular proliferation and vacuole biogenesis in epithelial cells. Cell. Microbiol. 4:4354.
141. Steele-Mortimer, O.,, L. A. Knodler,, S. L. Marcus,, M. P. Scheid,, B. Goh,, C. G. Pfeifer,, V. Duronio,, and B. B. Finlay. 2000. Activation of Akt/protein kinase B in epithelial cells by the Salmonella typhimurium effector sigD. J. Biol. Chem. 275:3771837724.
142. Stender, S.,, A. Friebel,, S. Linder,, M. Rohde,, S. Mirold,, and W. D. Hardt. 2000. Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell. Mol. Microbiol. 36:12061221.
143. Stuckey, J. A.,, H. L. Schubert,, E. B. Fauman,, Z. Y. Zhang,, J. E. Dixon,, and M. A. Saper. 1994. Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate. Nature 370:571575.
144. Sukhan, A.,, T. Kubori,, J. Wilson,, and J. E. Galan. 2001. Genetic analysis of assembly of the Salmonella enterica serovar Typhimurium type III secretion-associated needle complex. J. Bacteriol. 183:11591167.
145. Tamano, K.,, S. Aizawa,, E. Katayama,, T. Nonaka,, S. Imajoh-Ohmi,, A. Kuwae,, S. Nagai,, and C. Sasakawa. 2000. Supramolecular structure of the Shigella type III secretion machinery: the needle part is changeable in length and essential for delivery of effectors. EMBO J. 19:38763887.
146. Tardy, F.,, F. Homble,, C. Neyt,, R. Wattiez,, G. R. Cornelis,, J. M. Ruysschaert,, and V. Cabiaux. 1999. Yersinia enterocolitica type III secretion-translocation system: channel formation by secreted Yops. EMBO J. 18: 67936799.
147. Terebiznik, M. R.,, O. V. Vieira,, S. L. Marcus,, A. Slade,, C. M. Yip,, W. S. Trimble,, T. Meyer,, B. B. Finlay,, and S. Grinstein. 2002. Elimination of host cell PtdIns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella. Nat. Cell Biol. 4:766773.
148. Tezcan-Merdol, D.,, T. Nyman,, U. Lindberg,, F. Haag,, F. Koch-Nolte,, and M. Rhen. 2001. Actin is ADPribosylated by the Salmonella enterica virulence-associated protein SpvB. Mol. Microbiol. 39:606619.
149. Tsuge, H.,, M. Nagahama,, H. Nishimura,, J. Hisatsune,, Y. Sakaguchi,, Y. Itogawa,, N. Katunuma,, and J. Sakurai. 2003. Crystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens iota-toxin. J. Mol. Biol. 325:471483.
150. van Eerde, A.,, C. Hamiaux,, J. Perez,, C. Parsot,, and B. W. Dijkstra. 2004. Structure of Spa15, a type III secretion chaperone from Shigella flexneri with broad specificity. EMBO Rep. 5:477483.
151. Van Gijsegem, F.,, J. Vasse,, J. C. Camus,, M. Marenda,, and C. Boucher. 2000. Ralstonia solanacearum produces hrp-dependent pili that are required for PopA secretion but not for attachment of bacteria to plant cells. Mol. Microbiol. 36:249260.
152. Van Gijsegem, F.,, J. Vasse,, R. De Rycke,, P. Castello,, and C. Boucher. 2002. Genetic dissection of Ralstonia solanacearum hrp gene cluster reveals that the HrpV and HrpX proteins are required for Hrp pilus assembly. Mol. Microbiol. 44:935946.
153. Van Nhieu, G. T.,, and R. R. Isberg. 1991. The Yersinia pseudotuberculosis invasin protein and human fibronectin bind to mutually exclusive sites on the alpha 5 beta 1 integrin receptor. J. Biol. Chem. 266:2436724375.
154. Vetter, I. R.,, and A. Wittinghofer. 2001. The guanine nucleotide-binding switch in three dimensions. Science 294:12991304.
155. Wachter, C.,, C. Beinke,, M. Mattes,, and M. A. Schmidt. 1999. Insertion of EspD into epithelial target cell membranes by infecting enteropathogenic Escherichia coli. Mol. Microbiol. 31:16951707.
156. Wattiau, P.,, S. Woestyn,, and G. R. Cornelis. 1996. Customized secretion chaperones in pathogenic bacteria. Mol. Microbiol. 20:255262.
157. Wei, W.,, A. Plovanich-Jones,, W. L. Deng,, Q. L. Jin,, A. Collmer,, H. C. Huang,, and S. Y. He. 2000. The gene coding for the Hrp pilus structural protein is required for type III secretion of Hrp and Avr proteins in Pseudomonas syringae pv. tomato. Proc. Natl. Acad. Sci. USA 97:22472252.
158. Whitman, W. B.,, D. C. Coleman,, and W. J. Wiebe. 1998. Prokaryotes: the unseen majority. Proc. Natl. Acad. Sci. USA 95:65786583.
159. Wittinghofer, A.,, and E. F. Pai. 1991. The structure of Ras protein: a model for a universal molecular switch. Trends Biochem. Sci. 16:382387.
160. Woestyn, S.,, A. Allaoui,, P. Wattiau,, and G. R. Cornelis. 1994. YscN, the putative energizer of the Yersinia Yop secretion machinery. J. Bacteriol. 176:15611569.
161. Woestyn, S.,, M. P. Sory,, A. Boland,, O. Lequenne,, and G. R. Cornelis. 1996. The cytosolic SycE and SycH chaperones of Yersinia protect the region of YopE and YopH involved in translocation across eukaryotic cell membranes. Mol. Microbiol. 20:12611271.
162. Wood, M. W.,, R. Rosqvist,, P. B. Mullan,, M. H. Edwards,, and E. E. Galyov. 1996. SopE, a secreted protein of Salmonella dublin, is translocated into the target eukaryotic cell via a sip-dependent mechanism and promotes bacterial entry. Mol. Microbiol. 22:327338.
163. Worthylake, D. K.,, K. L. Rossman,, and J. Sondek. 2000. Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature 408:682688.
164. Wurtele, M.,, L. Renault,, J. T. Barbieri,, A. Wittinghofer,, and E. Wolf. 2001a. Structure of the ExoS GTPase activating domain. FEBS Lett. 491:2629.
165. Wurtele, M.,, E. Wolf,, K. J. Pederson,, G. Buchwald,, M. R. Ahmadian,, J. T. Barbieri,, and A. Wittinghofer. 2001b. How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat. Struct. Biol. 8:2326.
166. Yonekura, K.,, S. Maki-Yonekura,, and K. Namba. 2003. Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424:643650.
167. Young, V. B.,, V. L. Miller,, S. Falkow,, and G. K. Schoolnik. 1990. Sequence, localization and function of the invasin protein of Yersinia enterocolitica. Mol. Microbiol. 4:11191128.
168. Zaharik, M. L.,, S. Gruenheid,, A. J. Perrin,, and B. B. Finlay. 2002. Delivery of dangerous goods: type III secretion in enteric pathogens. Int. J. Med. Microbiol. 291:593603.
169. Zhang, S.,, R. L. Santos,, R. M. Tsolis,, S. Stender,, W. D. Hardt,, A. J. Baumler,, and L. G. Adams. 2002. The Salmonella enterica serotype Typhimurium effector proteins SipA, SopA, SopB, SopD, and SopE2 act in concert to induce diarrhea in calves. Infect. Immun. 70:38433855.
170. Zhang, Z. Y. 2002. Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development. Annu. Rev. Pharmacol. Toxicol. 42:209234.
171. Zhou, D.,, L. M. Chen,, L. Hernandez,, S. B. Shears,, and J. E. Galan. 2001. A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39:248259.
172. Zhou, D.,, and J. Galan. 2001. Salmonella entry into host cells: the work in concert of type III secreted effector proteins. Microbes Infect. 3:12931298.
173. Zhou, D.,, M. S. Mooseker,, and J. E. Galan. 1999a. An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc. Natl. Acad. Sci. USA 96:1017610181.
174. Zhou, D.,, M. S. Mooseker,, and J. E. Galan. 1999b. Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283:20922095.
175. Zumbihl, R.,, M. Aepfelbacher,, A. Andor,, C. A. Jacobi,, K. Ruckdeschel,, B. Rouot,, and J. Heesemann. 1999. The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA. J. Biol. Chem. 274:2928929293.

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