Assembly, structure, function and regulation of type III secretion systems

Nature Reviews Microbiology

Volumn 15, Issue 6, 2017, Pages 323-337

  Deng, Wanyin ^a   Marshall, Natalie C ^a,b   Rowland, Jennifer L ^a   McCoy, James M ^a   Worrall, Liam J ^b   Santos, Andrew S ^a,b   Strynadka, Natalie C J ^b   Finlay, B Brett ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; CHAPERONE; GLYCOSYLTRANSFERASE; SIGNAL PEPTIDE; VIRULENCE FACTOR; TYPE III SECRETION SYSTEM;

CELL CONTACT; GENE TRANSLOCATION; KINETOSOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN STRUCTURE, FUNCTION AND VARIABILITY; REGULATORY MECHANISM; REVIEW; TARGET CELL; TYPE III SECRETION SYSTEM; CELL MEMBRANE; CRYOELECTRON MICROSCOPY; FLAGELLUM; GRAM NEGATIVE BACTERIUM; METABOLISM; PHYSIOLOGY; PROTEIN TRANSPORT; ULTRASTRUCTURE;

CELL MEMBRANE; CRYOELECTRON MICROSCOPY; FLAGELLA; GRAM-NEGATIVE BACTERIA; PROTEIN TRANSPORT; TYPE III SECRETION SYSTEMS;

EID: 85017125583     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro.2017.20     Document Type: Review

References (144)

1. Costa, T. R. D. et al. Secretion systems in Gramnegative bacteria: structural and mechanistic insights. Nat. Rev. Microbiol. 13, 343-359 (2015).
2. Hueck, C. J. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62, 379-433 (1998).
3. Büttner, D. Protein export according to schedule: architecture, assembly, and regulation of type III secretion systems from plant-and animal-pathogenic bacteria. Microbiol. Mol. Biol. Rev. 76, 262-310 (2012).
4. Notti, R. Q. & Stebbins, C. E. The structure and function of type III secretion systems. Microbiol. Spectr. http://dx.doi.org/10.1128/microbiolspec. VMBF-0004-2015 (2015).
5. Portaliou, A. G., Tsolis, K. C., Loos, M. S., Zorzini, V. & Economou, A. Type III secretion: building and operating a remarkable nanomachine. Trends Biochem. Sci. 41, 175-189 (2016).
6. Abby, S. S. & Rocha, E. P. C. The non-flagellar type III secretion system evolved from the bacterial flagellum and diversified into host-cell adapted systems. PLoS Genet. 8, e1001983 (2012).
7. Michiels, T., Wattiau, P., Brasseur, R., Ruysschaert, J.-M. & Cornelis, G. Secretion of Yop proteins by Yersiniae. Infect. Immun. 58, 2840-2849 (1990).
8. Rosqvist, R., Forsberg, Å. & Wolf-Watz, H. Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. Infect. Immun. 59, 4562-4569 (1991).
9. van der Heijden, J. & Finlay, B. B. Type III effectormediated processes in Salmonella infection. Future Microbiol. 7, 685-670 (2012).
10. Raymond, B. et al. Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors. Trends Microbiol. 21, 430-441 (2013).
11. Büttner, D. Behind the lines-actions of bacterial type III effector proteins in plant cells. FEMS Microbiol. Rev. 40, 894-937 (2016).
12. Staehelin, C. & Krishnan, H. B. Nodulation outer proteins: double-edged swords of symbiotic rhizobia. Biochem. J. 470, 263-274 (2015).
13. Santos, A. S. & Finlay, B. B. Bringing down the host: enteropathogenic and enterohaemorrhagic Escherichia coli effector-mediated subversion of host innate immune pathways. Cell. Microbiol. 17, 318-332 (2015).
14. Bliska, J. B., Wang, X., Viboud, G. I. & Brodsky, I. E. Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors. Cell. Microbiol. 15, 1622-1631 (2013).
15. Beeckman, D. S. & Vanrompay, D. C. Bacterial secretion systems with an emphasis on the chlamydial type III secretion system. Curr. Issues Mol. Biol. 12, 17-41 (2010).
16. Miyata, S., Casey, M., Frank, D. W., Ausubel, F. M. & Drenkard, E. Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis. Infect. Immun. 71, 2404-2413 (2003).
17. Block, A. & Alfano, J. R. Plant targets for Pseudomonas syringae type III effectors: virulence targets or guarded decoys? Curr. Opin. Microbiol. 14, 39-46 (2011).
18. Gaytán, M. O., Martinez-Santos, V. I., Soto, E. & González-Pedrajo, B. Type three secretion system in attaching and effacing pathogens. Front. Cell. Infect. Microbiol. 6, 129 (2016).
19. Gazi, A. D. et al. Phylogenetic analysis of a gene cluster encoding an additional, rhizobial-like type III secretion system that is narrowly distributed among Pseudomonas syringae strains. BMC Microbiol. 12, 188 (2012).
20. Diepold, A. & Wagner, S. Assembly of the bacterial type III secretion machinery. FEMS Microbiol. Rev. 38, 802-822 (2014).
21. Kubori, T. et al. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280, 602-605 (1998).
22. Macnab, R. M. How bacteria assemble flagella. Annu. Rev. Microbiol. 57, 77-100 (2003).
23. Schraidt, O. & Marlovits, T. C. Three-dimensional model of Salmonella's needle complex at subnanometer resolution. Science 331, 1192-1195 (2011).
24. Cornelis, G. R. The type III secretion injectisome. Nat. Rev. Microbiol. 4, 811-825 (2006).
25. Burkinshaw, B. J. & Strynadka, N. C. J. Assembly and structure of the T3SS. Biochim. Biophys. Acta 1843, 1649-1663 (2014).
26. Schraidt, O. et al. Topology and organization of the Salmonella typhimurium type III secretion needle complex components. PLoS Pathog. 6, e1000824 (2010).
27. Hu, B. et al. Visualization of the type III secretion sorting platform of Shigella flexneri. Proc. Natl Acad. Sci. USA 112, 1047-1052 (2015).
28. Makino, F. et al. The architecture of the cytoplasmic region of type III secretion systems. Sci. Rep. 6, 33341 (2016).
29. Mueller, C. A. et al. The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310, 674-676 (2005).
30. Epler, C. R., Dickenson, N. E., Bullitt, E. & Picking, W. L. Ultrastructural analysis of IpaD at the tip of the nascent MxiH type III secretion apparatus of Shigella flexneri. J. Mol. Biol. 420, 29-39 (2012).
31. Journet, L., Agrain, C., Broz, P. & Cornelis, G. R. The needle length of bacterial injectisomes is determined by a molecular ruler. Science 302, 1757-1760 (2003).
32. Erhardt, M., Singer, H. M., Wee, D. H., Keener, J. P. & Hughes, K. T. An infrequent molecular ruler controls flagellar hook length in Salmonella enterica. EMBO J. 30, 2948-2961 (2011).
33. Monjaras Feria, J. et al. Role of EscP (Orf16) in injectisome biogenesis and regulation of type III protein secretion in enteropathogenic Escherichia coli. J. Bacteriol. 194, 6029-6045 (2012).
34. Wee, D. H. & Hughes, K. T. Molecular ruler determines needle length for the Salmonella Spi-1 injectisome. Proc. Natl Acad. Sci. USA 112, 4098-4103 (2015).
35. Parsot, C., Hamiaux, C. & Page, A. L. The various and varying roles of specific chaperones in type III secretion systems. Curr. Opin. Microbiol. 6, 7-14 (2003).
36. Thomas, N. A., Ma, I., Prasad, M. E. & Rafuse, C. Expanded roles for multicargo and class 1B effector chaperones in type III secretion. J. Bacteriol. 194, 3767-3773 (2012).
37. Kimbrough, T. G. & Miller, S. I. Contribution of Salmonella typhimurium type III secretion components to needle complex formation. Proc. Natl Acad. Sci. USA 97, 11008-11013 (2000).
38. Gauthier, A., Puente, J. L. & Finlay, B. B. Secretin of the enteropathogenic Escherichia coli type III secretion system requires components of the type III apparatus for assembly and localization. Infect. Immun. 71, 3310-3319 (2003).
39. Wagner, S. et al. Organization and coordinated assembly of the type III secretion export apparatus. Proc. Natl Acad. Sci. USA 107, 17745-17750 (2010).
40. Diepold, A. et al. Deciphering the assembly of the Yersinia type III secretion injectisome. EMBO J. 29, 1928-1940 (2010).
41. Yip, C. K. et al. Structural characterization of the molecular platform for type III secretion system assembly. Nature 435, 702-707 (2005).
42. Marlovits, T. C. et al. Structural insights into the assembly of the type III secretion needle complex. Science 306, 1040-1042 (2004).
43. Zilkenat, S. et al. Determination of the stoichiometry of the complete bacterial type III secretion needle complex using a combined quantitative proteomic approach. Mol. Cell. Proteomics 15, 1598-1609 (2016).
44. Dietsche, T. et al. Structural and functional characterization of the bacterial type III secretion export apparatus. PLoS Pathog. 12, e1006071 (2016).
45. Worrall, L. J. et al. Near-atomic resolution cryo-EM analysis of the Salmonella T3S injectisome basal body. Nature 540, 597-601 (2016).
46. Hodgkinson, J. L. et al. Three-dimensional reconstruction of the Shigella T3SS transmembrane regions reveals 12-fold symmetry and novel features throughout. Nat. Struct. Mol. Biol. 16, 477-485 (2009).
47. Kowal, J. et al. Structure of the dodecameric Yersinia enterocolitica secretin YscC and its trypsin-resistant core. Structure 21, 2152-2161 (2013).
48. Spreter, T. et al. A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system. Nat. Struct. Mol. Biol. 16, 468-476 (2009).
49. Bergeron, J. R. et al. A refined model of the prototypical Salmonella SPI-1 T3SS basal body reveals the molecular basis for its assembly. PLoS Pathog. 9, e1003307 (2013).
50. Abrusci, P. et al. Architecture of the major component of the type III secretion system export apparatus. Nat. Struct. Mol. Biol. 20, 99-104 (2013).
51. Zarivach, R. et al. Structural analysis of the essential self-cleaving type III secretion proteins EscU and SpaS. Nature 453, 124-127 (2008).
52. Deane, J. E. et al. Crystal structure of Spa40, the specificity switch for the Shigella flexneri type III secretion system. Mol. Microbiol. 69, 267-276 (2008).
53. Wiesand, U. et al. Structure of the type III secretion recognition protein YscU from Yersinia enterocolitica. J. Mol. Biol. 385, 854-866 (2009).
54. Kawamoto, A. et al. Common and distinct structural features of Salmonella injectisome and flagellar basal body. Sci. Rep. 3, 3369 (2013).
55. Kudryashev, M. et al. In situ structural analysis of the Yersinia enterocolitica injectisome. eLife 2, e00792 (2013).
56. Nans, A., Kudryashev, M., Saibil, H. R. & Hayward, R. D. Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nat. Commun. 6, 10114 (2015).
57. Lara-Tejero, M., Kato, J., Wagner, S., Liu, X. & Galán, J. E. A sorting platform determines the order of protein secretion in bacterial type III systems. Science 331, 1188-1191 (2011).
58. Diepold, A., Kudryashev, M., Delalez, N. J., Berry, R. M. & Armitage, P. Composition, formation, and regulation of the cytosolic C-ring, a dynamic component of the type III secretion injectisome. PLoS Biol. 13, e1002039 (2015).
59. Notti, R. Q., Bhattacharya, S., Lilic, M. & Stebbins, C. E. A common assembly module in injectisome and flagellar type III secretion sorting platforms. Nat. Commun. 7, 8125 (2015).
60. McDowell, M. A. et al. Characterization of Shigella Spa33 and Thermotoga FliM/N reveals a new model for C-ring assembly in T3SS. Mol. Microbiol. 99, 749-766 (2016).
61. Zarivach, R., Vuckovic, M., Deng, W., Finlay, B. B. & Strynadka, N. C. J. Structural analysis of a prototypical ATPase from the type III secretion system. Nat. Struct. Mol. Biol. 14, 131-137 (2007).
62. Imada, K., Minamino, T., Tahara, A. & Namba, K. Structural similarity between the flagellar type III ATPase FliI and F1-ATPase subunits. Proc. Natl Acad. Sci. USA 104, 485-490 (2007).
63. Imada, K., Minamino, T., Uchida, Y., Kinoshita, M. & Namba, K. Insight into the flagella type III export revealed by the complex structure of the type III ATPase and its regulator. Proc. Natl Acad. Sci. USA 113, 3633-3638 (2016).
64. Akeda, Y. & Galan, J. E. Chaperone release and unfolding of substrates in type III secretion. Nature 437, 911-915 (2005).
65. Marlovits, T. C. et al. Assembly of the inner rod determines needle length in the type III secretion injectisome. Nature 441, 637-640 (2006).
66. Loquet, A. et al. Atomic model of the type III secretion system needle. Nature 486, 276-279 (2012).
67. Demers, J.-P. et al. The common structural architecture of Shigella flexneri and Salmonella typhimurium type three secretion needles. PLoS Pathog. 9, e1003245 (2013).
68. Verasdonck, J. et al. Reassessment of MxiH subunit orientation and fold within native Shigella T3SS needles using surface labeling and solid-sate NMR. J. Struct. Biol. 192, 441-448 (2015).
69. Deane, J. E. et al. Molecular model of a type III secretion system needle: implications for host-cell sensing. Proc. Natl Acad. Sci. USA 103, 12529-12533 (2006).
70. Fujii, T. et al. Structure of a type III secretion needle at 7-Å resolution provides insights into its assembly and signaling mechanisms. Proc. Natl Acad. Sci. USA 109, 4461-4466 (2012).
71. Knutton, S. et al. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J. 17, 2166-2176 (1998).
72. Yip, C. K., Finlay, B. B. & Strynadka, N. C. J. Structural characterization of a type III secretion system filament protein in complex with its chaperone. Nat. Struct. Mol. Biol. 12, 75-81 (2005).
73. Jin, Q. & He, S.-Y. Role of the Hrp pilus in type III protein secretion in Pseudomonas syringae. Science 294, 2556-2558 (2001).
74. Li, C.-M. et al. The Hrp pilus of Pseudomonas syringae elongates from its tip and acts as a conduit for translocation of the effector protein HrpZ. EMBO J. 21, 1909-1915 (2002).
75. Romano, F. B. et al. Type 3 secretion translocators spontaneously assembles a hexadecameric transmembrane complex. J. Biol. Chem. 291, 6304-6315 (2016).
76. Sheahan, K.-L. & Isberg, R. R. Identification of mammalian proteins that collaborate with type III secretion system function: involvement of a chemokine receptor in supporting translocon activity. mBio 6, e02023-14 (2015).
77. Blondel, C. J. et al. CRISPR/Cas9 screens reveal requirements for host cell sulfation and fucosylation in bacterial type III secretion system-mediated cytotoxicity. Cell Host Microbe 20, 226-237 (2016).
78. Russo, B. C. et al. Intermediate filaments enable pathogen docking to trigger type 3 effector translocation. Nat. Microbiol. 1, 16025 (2016).
79. Deng, W. et al. Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proc. Natl Acad. Sci. USA 101, 3597-3602 (2004).
80. Burkinshaw, B. J. et al. Structural analysis of a specialized type III secretion system peptidoglycancleaving enzyme. J. Biol. Chem. 290, 10406-10417 (2015).
81. Creasey, E. A., Delahay, R. M., Daniell, S. J. & Frankel, G. Yeast two-hybrid system survey of interactions between LEE-encoded proteins of enteropathogenic Escherichia coli. Microbiology 149, 2093-2106 (2003).
82. Sorg, I. et al. YscU recognizes translocators as export substrates of the Yersinia injectisome. EMBO J. 26, 3015-3024 (2007).
83. Wood, S. E., Jin, J. & Lloyd, S. A. YscP and YscU switch the substrate specificity of the Yersinia type III secretion system by regulating export of the inner rod protein YscI. J. Bacteriol. 190, 5252-4263 (2008).
84. Sal-Man, N., Deng, W. & Finlay, B. B. EscI: a crucial component of the type III secretion system forms the inner rod structure in enteropathogenic Escherichia coli. Biochem. J. 442, 119-125 (2012).
85. Makishima, S., Komoriya, K., Yamaguchi, S. & Aizawa, S. I. Length of the flagellar hook and the capacity of the type III export apparatus. Science 291, 2411-2413 (2001).
86. Lefebre, M. D. & Galán, J. E. The inner rod protein controls substrate switching and needle length in a Salmonella type III secretion system. Proc. Natl Acad. Sci. USA 111, 817-822 (2014).
87. Nariya, M. K., Israeli, J., Shi, J. J. & Deeds, E. J. Mathematical model for length control by the timing of substrate switching in the type III secretion system. PLoS Comput. Biol. 12, e1004851 (2016).
88. Wagner, S., Stenta, M., Metzger, L. C., Dal Perato, M. & Cornelis, G. R. Length control of the injectisome needle requires only one molecule of Yop secretion protein P (YscP). Proc. Natl Acad. Sci. USA 107, 13860-13865 (2010).
89. Bergeron, J. R. et al. The structure of a type 3-secretion system (T3SS) ruler protein suggests a molecular mechanism for needle length sensing. J. Biol. Chem. 391, 1676-1691 (2016).
90. Mizuno, S., Amida, H., Kobayashi, N., Aizawa, S. & Tate, S. The NMR structure of FliK, the trigger for the switch of substrate specificity in the flagellar type III secretion apparatus. J. Mol. Biol. 409, 558-573 (2011).
91. Ho, O. et al. Characterization of the ruler protein interaction interface on the substrate specificity switch protein in the Yersinia type III secretion system. J. Biol. Chem. 292, 3299-3311 (2017).
92. Login, F. H. & Wolf-Watz, H. YscU/FlhB of Yersinia pseudotuberculosis harbors a C-terminal T3S signal. J. Biol. Chem. 290, 26282-26291 (2015).
93. Monjaras Feria, J. V., Lefebre, M. D., Stierhof, Y.-D., Galán, J. E. & Wagner, S. Role of autocleavage in the function of a type III secretion specificity switch protein in Salmonella enterica serovar Typhimurium. mBio 6, e01459-15 (2015).
94. Frost, S. et al. Autoproteolysis and intramolecular dissociation of Yersinia YscU precedes secretion of its C-terminal polypeptide YscUCC. PLoS ONE 7, e49349 (2012).
95. Cherradi, Y. et al. Interplay between predicted innerrod and gatekeeper in controlling substrate specificity of the type III secretion system. Mol. Microbiol. 87, 1183-1199 (2013).
96. Archuleta, T. L. & Spiller, B. W. A gatekeeper chaperone complex directs translocator secretion during type III secretion. PLoS Pathog. 10, e1004498 (2014).
97. Deng, W. et al. Regulation of type III secretion hierarchy of translocators and effectors in attaching and effacing bacterial pathogens. Infect. Immun. 73, 2135-2146 (2005).
98. Martinez-Argudo, I. & Blocker, A. J. The Shigella T3SS needle transmits a signal for MxiC release, which controls secretion of effectors. Mol. Microbiol. 78, 1365-1378 (2010).
99. Wang, D., Roe, A. J., McAteer, S., Shipston, M. J. & Gally, D. L. Hierarchal type III secretion of translocators and effectors from Escherichia coli O157:H7 requires the carboxy terminus of SepL that binds to Tir. Mol. Microbiol. 69, 1499-1512 (2008).
100. Yu, X. J., McGourty, K., Liu, M., Unsworth, K. E. & Holden, D. W. pH sensing by intracellular Salmonella induces effector translocation. Science 328, 1040-1043 (2010).
101. Armentrout, E. I. & Rietsch, A. The type III secretion translocation pore senses host cell contact. PLoS Pathog. 12, e1005530 (2016).
102. Mills, E., Baruch, K., Charpentier, X., Kobi, S. & Rosenshine, I. Real-time analysis of effector translocation by the type III secretion system of enteropathogenic Escherichia coli. Cell Host Microbe 3, 104-113 (2008).
103. Mills, E., Baruch, K., Aviv, G., Nitzan, M. & Rosenshine, I. Dynamics of the type III secretion system activity of enteropathogenic Escherichia coli. mBio 4, e00303-13 (2013).
104. Dewoody, R., Merritt, P. M., Houppert, A. S. & Marketon, M. M. YopK regulates the Yersinia pestis type III secretion system from within host cells. Mol. Microbiol. 79, 1445-1461 (2011).
105. Berger, C. N. et al. EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretion system protein translocation. mBio 3, e00317-12 (2012).
106. Radics, J., Königsmaier, L. & Marlovits, T. C. Structure of a pathogenic type 3 secretion system in action. Nat. Struct. Mol. Biol. 21, 82-87 (2014).
107. Arnold, R. et al. Sequence-based prediction of type III secreted proteins. PLoS Pathog. 5, e1000376 (2009).
108. Samudrala, R., Heffron, F. & McDermott, J. E. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems. PLoS Pathog. 5, 1000375 (2009).
109. McDermott, J. E. et al. Computational prediction of type III and IV secreted effectors in Gram-negative bacteria. Infect. Immun. 79, 23-32 (2011).
110. Anderson, D. M. & Schneewind, O. A. mRNA signal for the type III secretion of Yop proteins by Yersinia enterocolitica. Science 278, 1140-1143 (1997).
111. Anderson, D. M., Fouts, D. E., Collmer, A. & Schneewind, O. Reciprocal secretion of proteins by the bacterial type III machines of plant and animal pathogens suggests universal recognition of mRNA targeting signals. Proc. Natl Acad. Sci. USA 96, 12839-12843 (1999).
112. Lloyd, S. A., Norman, M., Rosqvist, R. & Wolf-Watz, H. Yersinia YopE is targeted for type III secretion by N-terminal, not mRNA, signals. Mol. Microbiol. 39, 520-531 (2001).
113. Lee, S. H. & Galan, J. E. Salmonella type III secretionassociated chaperones confer secretion-pathway specificity. Mol. Microbiol. 51, 483-495 (2004).
114. Deng, W., Yu, H. B., Li, Y. & Finlay, B. B. SepD/SepLdependent secretion signals of the type III secretion system translocator proteins in enteropathogenic Escherichia coli. J. Bacteriol. 197, 1263-1275 (2015).
115. Tomalka, A. G., Stopford, C. M., Lee, P.-C. & Rietsch, A. A translocator-specific export signal establishes the translocator-effector secretion hierarchy that is important for type III secretion system function. Mol. Microbiol. 86, 1464-1481 (2012).
116. Niemann, G. S. et al. RNA type III secretion signals that require Hfq. J. Bacteriol. 195, 2119-2125 (2013).
117. Stebbins, C. E. & Galan, J. E. Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion. Nature 414, 77-81 (2001).
118. Izore, T., Job, V. & Dessen, A. Biogenesis, regulation, and targeting of the type III secretion system. Structure 19, 603-612 (2011).
119. Dohlich, K., Zumsteg, A. B., Goosmann, C. & Kolbe, M. A substrate-fusion protein is trapped inside the type III secretion system channel in Shigella flexneri. PLoS Pathog. 10, e1003881 (2014).
120. Gauthier, A. & Finlay, B. B. Translocated intimin receptor and its chaperone interact with ATPase of the type III secretion apparatus of enteropathogenic Escherichia coli. J. Bacteriol. 185, 6747-6755 (2003).
121. Chen, L. et al. Substrate-activated conformational switch on chaperones encodes a targeting signal in type III secretion. Cell Rep. 3, 709-715 (2013).
122. Sorg, J. A., Blaylock, B. & Schneewind, O. Secretion signal recognition by YscN, the Yersinia type III secretion ATPase. Proc. Natl Acad. Sci. USA 103, 16490-16496 (2006).
123. Wilharm, G. et al. Yersinia enterocolitica type III secretion depends on the proton motive force but not on the flagellar motor components MotA and MotB. Infect. Immun. 72, 4004-4009 (2004).
124. Erhardt, M., Mertens, M. E., Fabiani, F. D. & Hughes, K. T. ATPase-independent type-III protein secretion in Salmonella enterica. PLoS Genet. 10, e1004800 (2014).
125. Rathinavelan, T. et al. A repulsive electrostatic mechanism for protein export through the type III secretion apparatus. Biophys. J. 98, 452-461 (2010).
126. Evans, L. D., Poulter, S., Terentjev, E. M., Hughes, C. & Fraser, G. M. A chain mechanism for flagellum growth. Nature 504, 287-290 (2013).
127. Galán, J. E., Lara-Tejero, M., Marlovits, T. C. & Wagner, S. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu. Rev. Microbiol. 68, 415-438 (2014).
128. Crepin, V. F., Shaw, R., Abe, C. M., Knutton, S. & Frankel, G. Polarity of enteropathogenic Escherichia coli EspA filament assembly and protein secretion. J. Bacteriol. 187, 2881-2889 (2005).
129. Akopyan, K. et al. Translocation of surface-localized effectors in type III secretion. Proc. Natl Acad. Sci. USA 108, 1639-1644 (2011).
130. Edgren, T., Forsberg, Å., Rosqvist, R. & Wolf-Watz, H. Type III secretion in Yersinia: injectisome or not? PLoS Pathog. 8, e1002669 (2012).
131. Marteyn, B. et al. Modulation of Shigella virulence in response to available oxygen in vivo. Nature 465, 355-358 (2010).
132. Wang, H. et al. Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science 353, 492-495 (2016).
133. Bahrani, F. K., Sansonetti, P. J. & Parsot, C. Secretion of Ipa proteins by Shigella flexneri: inducer molecules and kinetics of activation. Infect. Immun. 65, 4005-4010 (1997).
134. Kim, J. et al. Factors triggering type III secretion in Pseudomonas aeruginosa. Microbiology 151, 3575-3587 (2005).
135. Murillo, I., Martinez-Argudo, I. & Blocker, A. J. Genetic dissection of the signaling cascade that controls activation of the Shigella type III secretion system from the needle tip. Sci. Rep. 6, 27649 (2016).
136. Kenjale, R. et al. The needle component of the type III secretion of Shigella regulates the activity of the secretion apparatus. J. Biol. Chem. 280, 42929-42937 (2005).
137. Fernandez-Leiro, R. & Scheres, S. H. W. Unraveling biological macromolecules with cryo-electron microscopy. Nature 537, 339-346 (2016).
138. Marshall, N. C. & Finlay, B. B. Targeting the type III secretion system to treat bacterial infections. Expert Opin. Ther. Targets 18, 137-152 (2014).
139. Anantharajah, A., Mingeot-Leclercq, M.-P. & Van Bambeke, F. Targeting the type three secretion system in Pseudomonas aeruginosa. Trends Pharmacol. Sci. 37, 734-749 (2016).
140. Pallen, M. J., Beatson, S. A. & Bailey, C. M. Bioinformatics, genomics, and evolution of nonflagellar type-III secretion systems: a Darwinian perspective. FEMS Microbiol. Rev. 29, 201-229 (2005).
141. Sun, Y. H., Rolán, H. G. & Tsolis, R. M. Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium. J. Biol. Chem. 282, 33897-33901 (2007).
142. Du, J. et al. The type III secretion system apparatus determines the intracellular niche of bacterial pathogens. Proc. Natl Acad. Sci. USA 113, 4794-4799 (2016).
143. Soto, E. et al. Functional characterization of EscK (Orf4), a sorting platform component of the enteropathogenic Escherichia coli injectisome. J. Bacteriol. 199, e00538-16 (2017).
144. Tampakaki, A. P. Commonalities and differences of T3SSs in rhizobia and plant pathogenic bacteria. Front. Plant Sci. 5, 114 (2014).