A Sorting Platform Determines the Order of Protein Secretion in Bacterial Type III Systems
Abstract
Bacterial type III protein secretion systems deliver effector proteins into eukaryotic cells in order to modulate cellular processes. Central to the function of these protein-delivery machines is their ability to recognize and secrete substrates in a defined order. Here, we describe a mechanism by which a type III secretion system from the bacterial enteropathogen Salmonella enterica serovar Typhimurium can sort its substrates before secretion. This mechanism involves a cytoplasmic sorting platform that is sequentially loaded with the appropriate secreted proteins. The sequential loading of this platform, facilitated by customized chaperones, ensures the hierarchy in type III protein secretion. Given the presence of these machines in many important pathogens, these findings can serve as the bases for the development of novel antimicrobial strategies.
Get full access to this article
View all available purchase options and get full access to this article.
Already a Subscriber?Sign In
Supplementary Material
File (lara-tejero.som.pdf)
References and Notes
1
Galán J. E., Cossart P., Host-pathogen interactions: A diversity of themes, a variety of molecular machines. Curr. Opin. Microbiol. 8, 1 (2005).
2
Galán J. E., Wolf-Watz H., Protein delivery into eukaryotic cells by type III secretion machines. Nature 444, 567 (2006).
3
Alvarez-Martinez C. E., Christie P. J., Biological diversity of prokaryotic type IV secretion systems. Microbiol. Mol. Biol. Rev. 73, 775 (2009).
4
Pukatzki S., McAuley S. B., Miyata S. T., The type VI secretion system: Translocation of effectors and effector-domains. Curr. Opin. Microbiol. 12, 11 (2009).
5
Cornelis G. R., The type III secretion injectisome. Nat. Rev. Microbiol. 4, 811 (2006).
6
Kubori T., et al., Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 280, 602 (1998).
7
Håkansson 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 (1996).
8
Boland A., et al., Status of YopM and YopN in the Yersinia Yop virulon: YopM of Y.enterocolitica is internalized inside the cytosol of PU5-1.8 macrophages by the YopB, D, N delivery apparatus. EMBO J. 15, 5191 (1996).
9
Williams A. W., et al., Mutations in fliK and flhB affecting flagellar hook and filament assembly in Salmonella typhimurium. J. Bacteriol. 178, 2960 (1996).
10
Collazo C. M., Galán J. E., Requirement for exported proteins in secretion through the invasion-associated type III system of Salmonella typhimurium. Infect. Immun. 64, 3524 (1996).
11
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. U.S.A. 97, 10225 (2000).
12
Edqvist P. J., et al., YscP and YscU regulate substrate specificity of the Yersinia type III secretion system. J. Bacteriol. 185, 2259 (2003).
13
Riordan K. E., Sorg J. A., Berube B. J., Schneewind O., Impassable YscP substrates and their impact on the Yersinia enterocolitica type III secretion pathway. J. Bacteriol. 190, 6204 (2008).
14
Tamano K., Katayama E., Toyotome T., Sasakawa C., Shigella Spa32 is an essential secretory protein for functional type III secretion machinery and uniformity of its needle length. J. Bacteriol. 184, 1244 (2002).
15
Sorg J. A., Blaylock B., Schneewind O., Secretion signal recognition by YscN, the Yersinia type III secretion ATPase. Proc. Natl. Acad. Sci. U.S.A. 103, 16490 (2006).
16
Lara-Tejero M., Galán J. E., Salmonella enterica serovar typhimurium pathogenicity island 1-encoded type III secretion system translocases mediate intimate attachment to nonphagocytic cells. Infect. Immun. 77, 2635 (2009).
17
Kubori T., Galán J. E., Salmonella type III secretion-associated protein InvE controls translocation of effector proteins into host cells. J. Bacteriol. 184, 4699 (2002).
18
Galán J. E., Salmonella interactions with host cells: Type III secretion at work. Annu. Rev. Cell Dev. Biol. 17, 53 (2001).
19
Groisman E. A., Ochman H., Cognate gene clusters govern invasion of host epithelial cells by Salmonella typhimurium and Shigella flexneri. EMBO J. 12, 3779 (1993).
20
Minamino T., Imada K., Namba K., Mechanisms of type III protein export for bacterial flagellar assembly. Mol. Biosyst. 4, 1105 (2008).
21
Morita-Ishihara T., et al., Shigella Spa33 is an essential C-ring component of type III secretion machinery. J. Biol. Chem. 281, 599 (2006).
22
See Supporting Online Material for experimental details.
23
Schägger H., von Jagow G., Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal. Biochem. 199, 223 (1991).
24
Zierler M. K., Galán J. E., Contact with cultured epithelial cells stimulates secretion of Salmonella typhimurium invasion protein InvJ. Infect. Immun. 63, 4024 (1995).
25
Collazo C. M., Galán J. E., The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell. Mol. Microbiol. 24, 747 (1997).
26
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 (2001).
27
Feldman M. F., Cornelis G. R., The multitalented type III chaperones: All you can do with 15 kDa. FEMS Microbiol. Lett. 219, 151 (2003).
28
Stebbins C. E., Galán J. E., Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion. Nature 414, 77 (2001).
29
Kaniga K., Tucker S. C., Trollinger D., Galán J. E., Homologs of the Shigella IpaB and IpaC invasins are required for Salmonella typhimurium entry into cultured epithelial cells. J. Bacteriol. 177, 3965 (1995).
30
Journet L., et al., The needle length of bacterial injectisomes is determined by a molecular ruler. Science 302, 1757 (2003).
31
Marlovits T. C., et al., Assembly of the inner rod determines needle length in the type III secretion injectisome. Nature 441, 637 (2006).
32
González-Pedrajo B., Minamino T., Kihara M., Namba K., Interactions between C ring proteins and export apparatus components: A possible mechanism for facilitating type III protein export. Mol. Microbiol. 60, 984 (2006).
33
Jouihri N., et al., MxiK and MxiN interact with the Spa47 ATPase and are required for transit of the needle components MxiH and MxiI, but not of Ipa proteins, through the type III secretion apparatus of Shigella flexneri. Mol. Microbiol. 49, 755 (2003).
34
Johnson S., Blocker A., Characterization of soluble complexes of the Shigella flexneri type III secretion system ATPase. FEMS Microbiol. Lett. 286, 274 (2008).
35
Spaeth K. E., Chen Y. S., Valdivia R. H., The Chlamydia type III secretion system C-ring engages a chaperone-effector protein complex. PLoS Pathog. 5, e1000579 (2009).
Information & Authors
Information
Published In
Science
Volume 331 | Issue 6021
4 March 2011
4 March 2011
Copyright
Copyright © 2011, American Association for the Advancement of Science.
Article versions
You are viewing the most recent version of this article.
Submission history
Received: 9 December 2010
Accepted: 14 January 2011
Published in print: 4 March 2011
Acknowledgments
We thank members of the Galán laboratory for critical reading of this manuscript. This work was supported by NIH grant U54 AI0157158 (M.L.-T.), a long-term fellowship of the International Human Frontiers Science Program (S.W.), and NIH grant AI30492 (J.E.G.).
Authors
Metrics & Citations
Metrics
Article Usage
Altmetrics
Citations
Export citation
Select the format you want to export the citation of this publication.
Cited by
- Dynamic relocalization of cytosolic type III secretion system components prevents premature protein secretion at low external pH, Nature Communications, 12, 1, (2021).https://doi.org/10.1038/s41467-021-21863-4
- Secrete or perish: The role of secretion systems in Xanthomonas biology, Computational and Structural Biotechnology Journal, 19, (279-302), (2021).https://doi.org/10.1016/j.csbj.2020.12.020
- Substrate-engaged type III secretion system structures reveal gating mechanism for unfolded protein translocation, Nature Communications, 12, 1, (2021).https://doi.org/10.1038/s41467-021-21143-1
- Type 3 secretion system 1 of Salmonella typhimurium and its inhibitors: a novel strategy to combat salmonellosis, Environmental Science and Pollution Research, 28, 26, (34154-34166), (2021).https://doi.org/10.1007/s11356-021-13986-4
- Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei, Scientific Reports, 11, 1, (2021).https://doi.org/10.1038/s41598-021-89852-7
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria, Chemical Reviews, 121, 9, (5479-5596), (2021).https://doi.org/10.1021/acs.chemrev.1c00055
- Deciphering Legionella effector delivery by Icm/Dot secretion system reveals a new role for c-di-GMP signaling, Journal of Molecular Biology, 433, 13, (166985), (2021).https://doi.org/10.1016/j.jmb.2021.166985
- An elegant nano-injection machinery for sabotaging the host: Role of Type III secretion system in virulence of different human and animal pathogenic bacteria, Physics of Life Reviews, 38, (25-54), (2021).https://doi.org/10.1016/j.plrev.2021.05.007
- Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ ‐mediated suppression of the host cholesterol transport protein ABCA1 , Cellular Microbiology, 23, 8, (2021).https://doi.org/10.1111/cmi.13329
- Cryo-EM structure of the needle filament tip complex of the Salmonella type III secretion injectisome , Proceedings of the National Academy of Sciences, 118, 44, (e2114552118), (2021).https://doi.org/10.1073/pnas.2114552118
- See more
Loading...
View Options
Get Access
Log in to view the full text
AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.
- Become a AAAS Member
- Activate your AAAS ID
- Purchase Access to Other Journals in the Science Family
- Account Help
Log in via OpenAthens.
Log in via Shibboleth.
More options
Register for free to read this article
As a service to the community, this article is available for free. Login or register for free to read this article.
Buy a single issue of Science for just $15 USD.
View options
PDF format
Download this article as a PDF file
Download PDF