Abstract
Bacteria that have sustained long-standing close associations with eukaryotic hosts have evolved specific adaptations to survive and replicate in this environment. Perhaps one of the most remarkable of those adaptations is the type III secretion system (T3SS)—a bacterial organelle that has specifically evolved to deliver bacterial proteins into eukaryotic cells. Although originally identified in a handful of pathogenic bacteria, T3SSs are encoded by a large number of bacterial species that are symbiotic or pathogenic for humans, other animals including insects or nematodes, and plants. The study of these systems is leading to unique insights into not only organelle assembly and protein secretion but also mechanisms of symbiosis and pathogenesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pallen, M., Beatson, S. & Bailey, C. Bioinformatics, genomics and evolution of non-flagellar type-III secretion systems: a Darwinian perspective. FEMS Microbiol. Rev. 29, 201–229 (2005)
Saier, M. J. Evolution of bacterial type III protein secretion systems. Trends Microbiol. 12, 113–115 (2004)
Macnab, R. Type III flagellar protein export and flagellar assembly. Biochim. Biophys. Acta 1694, 207–217 (2004)
Cornelis, G. The Yersinia Ysc–Yop 'type III' weaponry. Nature Rev. Mol. Cell Biol. 3, 742–752 (2002)
Alfano, J. & Collmer, A. Type III secretion system effector proteins: double agents in bacterial disease and plant defense. Annu. Rev. Phytopathol. 42, 385–414 (2004)
Kubori, T. et al. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280, 602–605 (1998)
Blocker, A. et al. Structure and composition of the Shigella flexneri “needle complex”, a part of its type III secreton. Mol. Microbiol. 39, 652–663 (2001)
Sekiya, K. et al. 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, 11638–11643 (2001)
Daniell, S. et al. The filamentous type III secretion translocon of enteropathogenic Escherichia coli.. Cell. Microbiol. 3, 865–871 (2001)
Marlovits, T. C. et al. Structural insights into the assembly of the type III secretion needle complex. Science 306, 1040–1042 (2004)
Sukhan, A., Kubori, T., Wilson, J. & Galán, J. E. Genetic analysis of assembly of the Salmonella enterica serovar Typhimurium type III secretion-associated needle complex. J. Bacteriol. 183, 1159–1167 (2001)
Kubori, T., Sukhan, A., Aizawa, S. I. & Galán, J. E. Molecular characterization and assembly of the needle complex of the Salmonella typhimurium type III protein secretion system. Proc. Natl Acad. Sci. USA 97, 10225–10230 (2000)
Kimbrough, T. & Miller, S. Contribution of Salmonella typhimurium type III secretion components to needle complex formation. Proc. Natl Acad. Sci. USA 97, 11008–11013 (2000)
Crago, A. & Koronakis, V. Salmonella InvG forms a ring-like multimer that requires the InvH lipoprotein for outer membrane localization. Mol. Microbiol. 30, 47–56 (1998)
Daefler, S. & Russel, M. The Salmonella typhimurium InvH protein is an outer membrane lipoprotein required for the proper localization of InvG. Mol. Microbiol. 28, 1367–1380 (1998)
Crepin, V. et al. Structural and functional studies of the enteropathogenic Escherichia coli type III needle complex protein EscJ. Mol. Microbiol. 55, 1658–1670 (2005)
Yip, C. et al. Structural characterization of the molecular platform for type III secretion system assembly. Nature 435, 702–707 (2005)
Blocker, A., Komoriya, K. & Aizawa, S. Type III secretion systems and bacterial flagella: insights into their function from structural similarities. Proc. Natl Acad. Sci. USA 100, 3027–3030 (2003)
Morita-Ishihara, T. et al. Shigella Spa33 is an essential C-ring component of type III secretion machinery. J. Biol. Chem. 281, 599–560 (2006)
Li, J. et al. Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica.. Proc. Natl Acad. Sci. USA 92, 7252–7256 (1995)
Collazo, C. & Galán, J. E. Requirement of exported proteins for secretion through the invasion-associated Type III system in Salmonella typhimurium.. Infect. Immun. 64, 3524–3531 (1996)
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)
Hirano, T., Yamaguchi, S., Oosawa, K. & Aizawa, S. Roles of FliK and FlhB in determination of flagellar hook length in Salmonella typhimurium. J. Bacteriol. 176, 5439–5449 (1994)
Makishima, S., Komoriya, K., Yamaguchi, S. & Aizawa, S. Length of the flagellar hook and the capacity of the type III export apparatus. Science 291, 2411–2413 (2001)
Crepin, V., Shaw, R., Abe, C., Knutton, S. & Frankel, G. Polarity of enteropathogenic Escherichia coli EspA filament assembly and protein secretion. J. Bacteriol. 187, 2881–2889 (2005)
Marlovits, T. C. et al. Assembly of the inner rod determines needle length in the type III secretion injectisome. Nature 441, 637–640 (2006)
Edqvist, P. et al. YscP and YscU regulate substrate specificity of the Yersinia type III secretion system. J. Bacteriol. 185, 2259–2266 (2003)
West, N. et al. Optimization of virulence functions through glucosylation of Shigella LPS. Science 307, 1313–1317 (2005)
Mota, L. J., Journet, L., Sorg, I., Agrain, C. & Cornelis, G. R. Bacterial injectisomes: needle length does matter. Science 307, 1278 (2005)
Pettersson, J. et al. Modulation of virulence factor expression by pathogen target cell contact. Science 273, 1231–1233 (1996)
Wulff-Strobel, C., Williams, A. & Straley, S. LcrQ and SycH function together at the Ysc type III secretion system in Yersinia pestis to impose a hierarchy of secretion. Mol. Microbiol. 43, 411–423 (2002)
Sorg, J., Miller, N. & Schneewind, O. Substrate recognition of type III secretion machines–testing the RNA signal hypothesis. Cell. Microbiol. 7, 1217–1225 (2005)
Sory, M.-P., Boland, A., Lambermount, I. & Cornelis, G. 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, 11998–12002 (1995)
Schesser, K., Frithz-Lindsten, E. & Wolf-Watz, H. Delineation and mutational analysis of the Yersinia pseudotuberculosis YopE domains which mediate translocation across bacterial and eukaryotic cellular membranes. J. Bacteriol. 178, 7227–7233 (1996)
Anderson, D. M. & Schneewind, O. A mRNA signal for the type III secretion of Yop proteins by Yersinia enterocolitica.. Science 278, 1140–1143 (1997)
Lloyd, S., Sjöström, M., Andersson, S. & Wolf-Watz, H. Molecular characterization of type III secretion signals via analysis of synthetic N-terminal amino acid sequences. Mol. Microbiol. 43, 51–59 (2002)
Russmann, H., Kubori, T., Sauer, J. & Galán, J. Molecular and functional analysis of the type III secretion signal of the Salmonella enterica InvJ protein. Mol. Microbiol. 46, 769–779 (2002)
Lee, S. H. & Galán, J. E. Salmonella type III secretion-associated chaperones confer secretion-pathway specificity. Mol. Microbiol. 51, 483–495 (2004)
Wattiau, P. & Cornelis, G. R. SycE, a chaperone-like protein of Yersinia enterocolitica involved in the secretion of YopE. Mol. Microbiol. 8, 123–131 (1993)
Feldman, M. & Cornelis, G. The multitalented type III chaperones: all you can do with 15 kDa. FEMS Microbiol. Lett. 219, 151–158 (2003)
Stebbins, C. E. & Galán, J. E. Priming virulence factors for delivery into the host. Nature Rev. Mol. Biol. 4, 738–743 (2003)
Woestyn, S., Sory, M. P., Boland, A., Lequenne, O. & Cornelis, G. R. 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, 1261–1271 (1996)
Stebbins, C. E. & Galán, J. E. Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion. Nature 414, 77–81 (2001)
Birtalan, S. C., Phillips, R. M. & Ghosh, P. Three-dimensional secretion signals in chaperone-effector complexes of bacterial pathogens. Mol. Cell 9, 971–980 (2002)
Lilic, M., Vujanac, M. & Stebbins, C. A common structural motif in the binding of virulence factors to bacterial secretion chaperones. Mol. Cell 21, 653–664 (2006)
Luo, Y. et al. Structural and biochemical characterization of the type III secretion chaperones CesT and SigE. Nature Struct. Biol. 8, 1031–1036 (2001)
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)
Akeda, Y. & Galán, J. E. Chaperone release and unfolding of substrates in type III secretion. Nature 437, 911–915 (2005)
Muller, S. et al. Double hexameric ring assembly of the type III protein translocase ATPase HrcN. Mol. Microbiol. 61, 119–125 (2006)
Sauer, R. et al. Sculpting the proteome with AAA+ proteases and disassembly machines. Cell 119, 9–18 (2004)
Hoiczyk, E. & Blobel, G. Polymerization of a single protein of the pathogen Yersinia enterocolitica into needles punctures eukaryotic cells. Proc. Natl Acad. Sci. USA 98, 4669–4674 (2001)
Sory, M.-P. & Cornelis, G. R. Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol. Microbiol. 14, 583–594 (1994)
Hakansson, S. et al. 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, 5812–5823 (1996)
Tardy, F. et al. Yersinia enterocolitica type III secretion-translocation system: channel formation by secreted Yops. EMBO J. 18, 6793–6799 (1999)
Mueller, C. et al. The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310, 674–676 (2005)
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)
Roine, E. et al. Hrp pilus: an hrp-dependent bacterial surface appendage produced by Pseudomonas syringae pv. tomato DC3000. Proc. Natl Acad. Sci. USA 94, 3459–3464 (1997)
Francis, M., Wolf-Watz, H. & Forsberg, A. Regulation of type III secretion systems. Curr. Opin. Microbiol. 5, 166–172 (2002)
Ménard, R., Sansonetti, P. J. & Parsot, C. The secretion of the Shigella flexneri Ipa invasins is induced by the epithelial cell and controlled by IpaB and IpaD. EMBO J. 13, 5293–5302 (1994)
Torruellas, J., Jackson, M., Pennock, J. & Plano, G. The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion. Mol. Microbiol. 57, 1719–1733 (2005)
Kenjale, R. et al. The needle component of the type III secreton of Shigella regulates the activity of the secretion apparatus. J. Biol. Chem. 280, 42929–42937 (2005)
Cordes, F. et al. Helical packing of needles from functionally altered Shigella type III secretion systems. J. Mol. Biol. 354, 206–211 (2005)
Iriarte, M. et al. TyeA, a protein involved in control of Yop release and in translocation of Yersinia Yop effectors. EMBO J. 17, 1907–1918 (1998)
Day, J. & Plano, G. A complex composed of SycN and YscB functions as a specific chaperone for YopN in Yersinia pestis. Mol. Microbiol. 30, 777–788 (1998)
Schubot, F. et al. Three-dimensional structure of a macromolecular assembly that regulates type III secretion in Yersinia pestis. J. Mol. Biol. 346, 1147–1161 (2005)
Kubori, T. & Galán, J. E. Salmonella type III secretion-associated protein InvE controls translocation of effector proteins into host cells. J. Bacteriol. 184, 4699–4708 (2002)
O'Connell, C. et al. SepL, a protein required for enteropathogenic Escherichia coli type III translocation, interacts with secretion component SepD. Mol. Microbiol. 52, 1613–1625 (2004)
Demers, B., Sansonetti, P. J. & Parsot, C. Induction of type III secretion in Shigella flexneri is associated with differential control of transcription of genes encoding secreted proteins. EMBO J. 17, 2894–2903 (1998)
Parsot, C. et al. A secreted anti-activator, OspD1, and its chaperone, Spa15, are involved in the control of transcription by the type III secretion apparatus activity in Shigella flexneri. Mol. Microbiol. 56, 1627–1635 (2005)
Rietsch, A., Vallet-Gely, I., Dove, S. & Mekalanos, J. ExsE, a secreted regulator of type III secretion genes in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 102, 8006–8011 (2005)
Urbanowski, M., Lykken, G. & Yahr, T. A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system. Proc. Natl Acad. Sci. USA 102, 9930–9935 (2005)
Hughes, K. T., Gillen, K. L., Semon, M. J. & Karlinsey, J. E. Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator. Science 262, 1277–1280 (1993)
Stebbins, C. E. & Galán, J. E. Structural mimicry in bacterial virulence. Nature 412, 701–705 (2001)
Hardt, W.-D., Chen, L.-M., Schuebel, K. E., Bustelo, X. R. & Galán, J. E. Salmonella typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93, 815–826 (1998)
Buchwald, G. et al. Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J. 21, 3286–3295 (2002)
Fu, Y. & Galán, J. E. A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401, 293–297 (1999)
Von Pawel-Rammingen, U. et al. GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure. Mol. Microbiol. 36, 737–748 (2000)
Goehring, U., Schmidt, G., Pederson, K., Aktories, K. & Barbieri, J. The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J. Biol. Chem. 274, 36369–36372 (1999)
Stebbins, C. E. & Galán, J. E. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1. Mol. Cell 6, 1449–1460 (2000)
Wurtele, M. et al. How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nature Struct. Biol. 8, 23–26 (2001)
Kubori, T. & Galán, J. E. Temporal regulation of Salmonella virulence effector function by proteasome-dependent protein degradation. Cell 115, 333–342 (2003)
Kim, M. et al. Two Pseudomonas syringae type III effectors inhibit RIN4-regulated basal defense in Arabidopsis.. Cell 121, 749–759 (2005)
Nordfelth, R., Kauppi, A., Norberg, H., Wolf-Watz, H. & Elofsson, M. Small-molecule inhibitors specifically targeting type III secretion. Infect. Immun. 73, 3104–3114 (2005)
Russmann, H. et al. Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 281, 565–568 (1998)
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Galán, J., Wolf-Watz, H. Protein delivery into eukaryotic cells by type III secretion machines. Nature 444, 567–573 (2006). https://doi.org/10.1038/nature05272
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature05272
This article is cited by
-
Site-Directed Spin Label EPR Studies of the Structure and Membrane Interactions of the Bacterial Phospholipase ExoU
Applied Magnetic Resonance (2024)
-
Review of Pseudomonas species causing bacterial canker of Prunus species with emphasis on sweet cherry (Prunus avium) in New Zealand
European Journal of Plant Pathology (2024)
-
Development of recombinant subunit vaccine targeting InvH protein of Salmonella Typhimurium and evaluation of its immunoprotective efficacy against salmonellosis
Brazilian Journal of Microbiology (2023)
-
Orf1B controls secretion of T3SS proteins and contributes to Edwardsiella piscicida adhesion to epithelial cells
Veterinary Research (2022)
-
Comparative transcriptomic analysis provides insights into transcription mechanisms of Vibrio parahaemolyticus T3SS during interaction with HeLa cells
Brazilian Journal of Microbiology (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.