Activation of Shigella flexneri type 3 secretion requires a host-induced conformational change to the translocon pore


Autoři: Brian C. Russo aff001;  Jeffrey K. Duncan aff001;  Alexandra L. Wiscovitch aff001;  Austin C. Hachey aff001;  Marcia B. Goldberg aff001
Působiště autorů: Center for Bacterial Pathogenesis, Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America aff001;  Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America aff002;  Research Scholar Initiative, The Graduate School of Arts and Sciences, Harvard University, Cambridge, Massachusetts, United States of America aff003
Vyšlo v časopise: Activation of Shigella flexneri type 3 secretion requires a host-induced conformational change to the translocon pore. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1007928
Kategorie: Research Article
doi: 10.1371/journal.ppat.1007928

Souhrn

Type 3 secretion systems (T3SSs) are conserved bacterial nanomachines that inject virulence proteins (effectors) into eukaryotic cells during infection. Due to their ability to inject heterologous proteins into human cells, these systems are being developed as therapeutic delivery devices. The T3SS assembles a translocon pore in the plasma membrane and then docks onto the pore. Docking activates effector secretion through the pore and into the host cytosol. Here, using Shigella flexneri, a model pathogen for the study of type 3 secretion, we determined the molecular mechanisms by which host intermediate filaments trigger docking and enable effector secretion. We show that the interaction of intermediate filaments with the translocon pore protein IpaC changed the pore’s conformation in a manner that was required for docking. Intermediate filaments repositioned residues of the Shigella pore protein IpaC that are located on the surface of the pore and in the pore channel. Restricting these conformational changes blocked docking in an intermediate filament-dependent manner. These data demonstrate that a host-induced conformational change to the pore enables T3SS docking and effector secretion, providing new mechanistic insight into the regulation of type 3 secretion.

Klíčová slova:

Cell membranes – Cross-linking – Cysteine – Membrane proteins – Secretion – Secretion systems – Shigella flexneri – Intermediate filaments


Zdroje

1. Cheung M, Shen DK, Makino F, Kato T, Roehrich AD, Martinez-Argudo I, et al. Three-dimensional electron microscopy reconstruction and cysteine-mediated crosslinking provide a model of the type III secretion system needle tip complex. Molecular microbiology. 2015;95(1):31–50. doi: 10.1111/mmi.12843 25353930.

2. Epler CR, Dickenson NE, Bullitt E, Picking WL. Ultrastructural analysis of IpaD at the tip of the nascent MxiH type III secretion apparatus of Shigella flexneri. J Mol Biol. 2012;420(1–2):29–39. Epub 2012/04/07. doi: 10.1016/j.jmb.2012.03.025 22480614.

3. Veenendaal AK, Hodgkinson JL, Schwarzer L, Stabat D, Zenk SF, Blocker AJ. The type III secretion system needle tip complex mediates host cell sensing and translocon insertion. Molecular microbiology. 2007;63(6):1719–30. Epub 2007/03/21. doi: 10.1111/j.1365-2958.2007.05620.x 17367391.

4. Hu Y, Huang H, Cheng X, Shu X, White AP, Stavrinides J, et al. A global survey of bacterial type III secretion systems and their effectors. Environ Microbiol. 2017;19(10):3879–95. doi: 10.1111/1462-2920.13755 28401683.

5. Faudry E, Vernier G, Neumann E, Forge V, Attree I. Synergistic pore formation by type III toxin translocators of Pseudomonas aeruginosa. Biochemistry. 2006;45(26):8117–23. Epub 2006/06/28. doi: 10.1021/bi060452+ 16800636.

6. Blocker A, Gounon P, Larquet E, Niebuhr K, Cabiaux V, Parsot C, et al. The tripartite type III secreton of Shigella flexneri inserts IpaB and IpaC into host membranes. J Cell Biol. 1999;147(3):683–93. Epub 1999/11/05. doi: 10.1083/jcb.147.3.683 10545510.

7. Russo BC, Stamm LM, Raaben M, Kim CM, Kahoud E, Robinson LR, et al. Intermediate filaments enable pathogen docking to trigger type 3 effector translocation. Nat Micro. 2016;1:16025.

8. Scherer CA, Cooper E, Miller SI. The Salmonella type III secretion translocon protein SspC is inserted into the epithelial cell plasma membrane upon infection. Molecular microbiology. 2000;37(5):1133–45. Epub 2000/09/06. doi: 10.1046/j.1365-2958.2000.02066.x 10972831.

9. Carlson SA, Omary MB, Jones BD. Identification of cytokeratins as accessory mediators of Salmonella entry into eukaryotic cells. Life Sci. 2002;70(12):1415–26. Epub 2002/03/09. doi: 10.1016/s0024-3205(01)01512-0 11883717.

10. Armentrout EI, Rietsch A. The Type III Secretion Translocation Pore Senses Host Cell Contact. PLoS pathogens. 2016;12(3):e1005530. doi: 10.1371/journal.ppat.1005530 27022930.

11. Nans A, Kudryashev M, Saibil HR, Hayward RD. Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nature communications. 2015;6:10114. doi: 10.1038/ncomms10114 26656452.

12. Hu B, Lara-Tejero M, Kong Q, Galan JE, Liu J. In Situ Molecular Architecture of the Salmonella Type III Secretion Machine. Cell. 2017;168(6):1065–74.e10. doi: 10.1016/j.cell.2017.02.022 28283062.

13. Park D, Lara-Tejero M, Waxham MN, Li W, Hu B, Galan JE, et al. Visualization of the type III secretion mediated Salmonella-host cell interface using cryo-electron tomography. Elife. 2018;7. Epub 2018/10/04. doi: 10.7554/eLife.39514 30281019.

14. Adams W, Morgan J, Kwuan L, Auerbuch V. Yersinia pseudotuberculosis YopD mutants that genetically separate effector protein translocation from host membrane disruption. Molecular microbiology. 2015;96(4):764–78. Epub 2015/02/17. doi: 10.1111/mmi.12970 25684661.

15. Kenjale R, Wilson J, Zenk SF, Saurya S, Picking WL, Picking WD, et al. The needle component of the type III secreton of Shigella regulates the activity of the secretion apparatus. The Journal of biological chemistry. 2005;280(52):42929–37. Epub 2005/10/18. doi: 10.1074/jbc.M508377200 16227202.

16. Guo EZ, Desrosiers DC, Zalesak J, Tolchard J, Berbon M, Habenstein B, et al. A polymorphic helix of a Salmonella needle protein relays signals defining distinct steps in type III secretion. PLoS Biol. 2019;17(7):e3000351. Epub 2019/07/02. doi: 10.1371/journal.pbio.3000351 31260457.

17. Martinez-Argudo I, Blocker AJ. The Shigella T3SS needle transmits a signal for MxiC release, which controls secretion of effectors. Molecular microbiology. 2010;78(6):1365–78. Epub 2010/12/15. doi: 10.1111/j.1365-2958.2010.07413.x 21143311.

18. Lara-Tejero M, Kato J, Wagner S, Liu X, Galan JE. A sorting platform determines the order of protein secretion in bacterial type III systems. Science. 2011;331(6021):1188–91. doi: 10.1126/science.1201476 21292939.

19. Hu B, Morado DR, Margolin W, Rohde JR, Arizmendi O, Picking WL, et al. Visualization of the type III secretion sorting platform of Shigella flexneri. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(4):1047–52. doi: 10.1073/pnas.1411610112 25583506.

20. Hume PJ, McGhie EJ, Hayward RD, Koronakis V. The purified Shigella IpaB and Salmonella SipB translocators share biochemical properties and membrane topology. Molecular microbiology. 2003;49(2):425–39. doi: 10.1046/j.1365-2958.2003.03559.x 12828640.

21. Montagner C, Arquint C, Cornelis GR. Translocators YopB and YopD from Yersinia enterocolitica form a multimeric integral membrane complex in eukaryotic cell membranes. Journal of bacteriology. 2011;193(24):6923–8. Epub 2011/10/18. doi: 10.1128/JB.05555-11 22001511.

22. Ide T, Laarmann S, Greune L, Schillers H, Oberleithner H, Schmidt MA. Characterization of translocation pores inserted into plasma membranes by type III-secreted Esp proteins of enteropathogenic Escherichia coli. Cellular microbiology. 2001;3(10):669–79. doi: 10.1046/j.1462-5822.2001.00146.x 11580752.

23. Russo BC, Duncan JK, Goldberg MB. Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection. mBio. 2019;10:e00877–19. doi: 10.1128/mBio.00877-19 31138750

24. Lai WC, Hazelbauer GL. Analyzing transmembrane chemoreceptors using in vivo disulfide formation between introduced cysteines. Methods in enzymology. 2007;423:299–316. Epub 2007/07/05. doi: 10.1016/S0076-6879(07)23013-7 17609137.

25. Viboud GI, Bliska JB. Measurement of pore formation by contact-dependent type III protein secretion systems. Methods in enzymology. 2002;358:345–50. doi: 10.1016/s0076-6879(02)58100-3 12474398.

26. Wang F, Chan C, Weir NR, Denic V. The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase. Nature. 2014;512(7515):441–4. doi: 10.1038/nature13471 25043001.

27. Harrington A, Darboe N, Kenjale R, Picking WL, Middaugh CR, Birket S, et al. Characterization of the interaction of single tryptophan containing mutants of IpaC from Shigella flexneri with phospholipid membranes. Biochemistry. 2006;45(2):626–36. doi: 10.1021/bi0512593 16401091.

28. Lara-Tejero M, Galan JE. Salmonella enterica serovar typhimurium pathogenicity island 1-encoded type III secretion system translocases mediate intimate attachment to nonphagocytic cells. Infection and immunity. 2009;77(7):2635–42. Epub 2009/04/15. doi: 10.1128/IAI.00077-09 19364837.

29. Enninga J, Mounier J, Sansonetti P, Tran Van Nhieu G. Secretion of type III effectors into host cells in real time. Nat Methods. 2005;2(12):959–65. doi: 10.1038/nmeth804 16299482.

30. Lee VT, Mazmanian SK, Schneewind O. A program of Yersinia enterocolitica type III secretion reactions is activated by specific signals. Journal of bacteriology. 2001;183(17):4970–8. Epub 2001/08/08. doi: 10.1128/JB.183.17.4970-4978.2001 11489848.

31. Torruellas J, Jackson MW, Pennock JW, Plano GV. The Yersinia pestis type III secretion needle plays a role in the regulation of Yop secretion. Molecular microbiology. 2005;57(6):1719–33. Epub 2005/09/02. doi: 10.1111/j.1365-2958.2005.04790.x 16135236.

32. Radics J, Konigsmaier L, Marlovits TC. Structure of a pathogenic type 3 secretion system in action. Nat Struct Mol Biol. 2014;21(1):82–7. doi: 10.1038/nsmb.2722 24317488.

33. Mounier J, Popoff MR, Enninga J, Frame MC, Sansonetti PJ, Van Nhieu GT. The IpaC carboxyterminal effector domain mediates Src-dependent actin polymerization during Shigella invasion of epithelial cells. PLoS pathogens. 2009;5(1):e1000271. doi: 10.1371/journal.ppat.1000271 19165331.

34. Yu XJ, McGourty K, Liu M, Unsworth KE, Holden DW. pH sensing by intracellular Salmonella induces effector translocation. Science. 2010;328(5981):1040–3. Epub 2010/04/17. doi: 10.1126/science.1189000 20395475.

35. van der Goot FG, Tran van Nhieu G, Allaoui A, Sansonetti P, Lafont F. Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism. The Journal of biological chemistry. 2004;279(46):47792–8. doi: 10.1074/jbc.M406824200 15364928.

36. Lafont F, Tran Van Nhieu G, Hanada K, Sansonetti P, van der Goot FG. Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. The EMBO journal. 2002;21(17):4449–57. doi: 10.1093/emboj/cdf457 12198147.

37. Campbell-Valois FX, Schnupf P, Nigro G, Sachse M, Sansonetti PJ, Parsot C. A fluorescent reporter reveals on/off regulation of the Shigella type III secretion apparatus during entry and cell-to-cell spread. Cell host & microbe. 2014;15(2):177–89. doi: 10.1016/j.chom.2014.01.005 24528864.

38. Terry CM, Picking WL, Birket SE, Flentie K, Hoffman BM, Barker JR, et al. The C-terminus of IpaC is required for effector activities related to Shigella invasion of host cells. Microbial pathogenesis. 2008;45(4):282–9. Epub 2008/07/29. doi: 10.1016/j.micpath.2008.06.003 18656530.

39. Yang CY, Chang PW, Hsu WH, Chang HC, Chen CL, Lai CC, et al. Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration. Oncogene. 2019;38(21):4075–94. Epub 2019/01/31. doi: 10.1038/s41388-019-0705-x 30696956.

40. Du J, Reeves AZ, Klein JA, Twedt DJ, Knodler LA, Lesser CF. The type III secretion system apparatus determines the intracellular niche of bacterial pathogens. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(17):4794–9. doi: 10.1073/pnas.1520699113 27078095.

41. Osiecki JC, Barker J, Picking WL, Serfis AB, Berring E, Shah S, et al. IpaC from Shigella and SipC from Salmonella possess similar biochemical properties but are functionally distinct. Molecular microbiology. 2001;42(2):469–81. Epub 2001/11/13. doi: 10.1046/j.1365-2958.2001.02654.x 11703668.

42. Colucci-Guyon E, Portier MM, Dunia I, Paulin D, Pournin S, Babinet C. Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell. 1994;79(4):679–94. Epub 1994/11/18. doi: 10.1016/0092-8674(94)90553-3 7954832.

43. Lu R, Herrera BB, Eshleman HD, Fu Y, Bloom A, Li Z, et al. Shigella Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation. PLoS pathogens. 2015;11(10):e1005200. Epub 2015/10/17. doi: 10.1371/journal.ppat.1005200 26473364.

44. Garza-Mayers AC, Miller KA, Russo BC, Nagda DV, Goldberg MB. Shigella flexneri regulation of ARF6 activation during bacterial entry via an IpgD-mediated positive feedback loop. MBio. 2015;6(2):e02584. Epub 2015/03/05. doi: 10.1128/mBio.02584-14 25736891.

45. Labigne-Roussel AF, Lark D, Schoolnik G, Falkow S. Cloning and expression of an afimbrial adhesin (AFA-I) responsible for P blood group-independent, mannose-resistant hemagglutination from a pyelonephritic Escherichia coli strain. Infection and immunity. 1984;46(1):251–9. 6148308.

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Hygiena a epidemiologie Infekční lékařství Laboratoř

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