1. Microbiology and Infectious Disease
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An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell

  1. Michael J Coffey
  2. Brad E Sleebs
  3. Alessandro D Uboldi
  4. Alexandra L Garnham
  5. Magdalena Franco
  6. Nicole D Marino
  7. Michael W Panas
  8. David JP Ferguson
  9. Marta Enciso
  10. Matthew T O'Neill
  11. Sash Lopaticki
  12. Rebecca J Stewart
  13. Grant Dewson
  14. Gordon K Smyth
  15. Brian J Smith
  16. Seth L Masters
  17. John C Boothroyd
  18. Justin A Boddey
  19. Christopher J Tonkin  Is a corresponding author
  1. The Walter and Eliza Hall Institute of Medical Research, Australia
  2. Stanford University School of Medicine, United States
  3. University of Oxford, United Kingdom
  4. La Trobe University, Australia
  5. Walter and Eliza Hall Institute of Medical Research, Australia
Research Article
  • Cited 46
  • Views 3,310
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Cite this article as: eLife 2015;4:e10809 doi: 10.7554/eLife.10809

Abstract

Infection by Toxoplasma gondii leads to massive changes to the host cell. Here we identify a novel host cell effector export pathway, which requires the Golgi-resident Aspartyl Protease 5 (ASP5). We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has similarity to the PEXEL-motif of Plasmodium parasites. We show that ASP5 matures substrates at both the N- and C-terminal ends of proteins and also controls trafficking of effectors without this motif. Furthermore, ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the vacuole. Assessment of host gene expression reveals that the ASP5-dependent pathway influences thousands of the transcriptional changes that Toxoplasma imparts on its host cell. All these changes result in attenuation of virulence of Δasp5 tachyzoites in vivo. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell.

Article and author information

Author details

  1. Michael J Coffey

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Brad E Sleebs

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Alessandro D Uboldi

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandra L Garnham

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Magdalena Franco

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Nicole D Marino

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael W Panas

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. David JP Ferguson

    Nuffield Department of Clinical Laboratory Science, University of Oxford, Oxoford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Marta Enciso

    La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Matthew T O'Neill

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  11. Sash Lopaticki

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  12. Rebecca J Stewart

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  13. Grant Dewson

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Gordon K Smyth

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Brian J Smith

    La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Seth L Masters

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. John C Boothroyd

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Justin A Boddey

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Christopher J Tonkin

    Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    For correspondence
    tonkin@wehi.edu.au
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments complied with the regulatory standards of and were approved by the Walter and Eliza Hall Institute Animal Ethics Committees under approval number 2014.019.

Reviewing Editor

  1. Axel A Brakhage, Friedrich Schiller University Jena and Hans-Knöll-Institut, Germany

Publication history

  1. Received: August 13, 2015
  2. Accepted: November 18, 2015
  3. Accepted Manuscript published: November 18, 2015 (version 1)
  4. Version of Record published: February 10, 2016 (version 2)

Copyright

© 2015, Coffey et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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