1. Microbiology and Infectious Disease
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Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase

  1. Azadeh Seidi
  2. Linden S Muellner-Wong
  3. Esther Rajendran
  4. Edwin T Tjhin
  5. Laura Dagley
  6. Vincent YT Aw
  7. Pierre Faou
  8. Andrew I Webb
  9. Christopher J Tonkin
  10. Giel G van Dooren  Is a corresponding author
  1. Australian National University, Australia
  2. The Walter and Eliza Hall Institute of Medical Research, Australia
  3. La Trobe University, Australia
Research Article
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Cite this article as: eLife 2018;7:e38131 doi: 10.7554/eLife.38131

Abstract

The mitochondrion of apicomplexan parasites is critical for parasite survival, although the full complement of proteins that localize to this organelle has not been defined. Here we undertake two independent approaches to elucidate the mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify approximately 400 mitochondrial proteins, many of which lack homologs in the animals that these parasites infect, and most of which are important for parasite growth. We demonstrate that one such protein, termed TgApiCox25, is an important component of the parasite cytochrome c oxidase (COX) complex. We identify numerous other apicomplexan-specific components of COX, and conclude that apicomplexan COX, and apicomplexan mitochondria more generally, differ substantially in their protein composition from the hosts they infect. Our study highlights the diversity that exists in mitochondrial proteomes across the eukaryotic domain of life, and provides a foundation for defining unique aspects of mitochondrial biology in an important phylum of parasites.

Data availability

Mitochondrial proteomics data is available in on the ToxoDB website (http://toxodb.org).

The following data sets were generated

Article and author information

Author details

  1. Azadeh Seidi

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Linden S Muellner-Wong

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0348-6408
  3. Esther Rajendran

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Edwin T Tjhin

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Laura Dagley

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Vincent YT Aw

    Research School of Biology, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Pierre Faou

    Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Andrew I Webb

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

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Giel G van Dooren

    Research School of Biology, Australian National University, Canberra, Australia
    For correspondence
    giel.vandooren@anu.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2455-9821

Funding

Australian Research Council (DP110103144)

  • Giel G van Dooren

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: May 6, 2018
  2. Accepted: September 9, 2018
  3. Accepted Manuscript published: September 11, 2018 (version 1)
  4. Version of Record published: September 25, 2018 (version 2)

Copyright

© 2018, Seidi 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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Further reading

    1. Microbiology and Infectious Disease
    Nicholas Rinkenberger et al.
    Research Article Updated

    Toxoplasma gondii is an important human pathogen infecting an estimated one in three people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restricting T. gondii growth in human cells. Growth restriction is presumed to be due to the induction of interferon-stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impact T. gondii infection in human cells. In addition to IRF1, which likely acts through the induction of numerous downstream genes, we identified RARRES3 as a single factor that restricts T. gondii infection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restricting T. gondii infection, the limited number of ISGs capable of restricting T. gondii infection when individually expressed suggests that IFNγ-mediated immunity to T. gondii infection is a complex, multifactorial process.

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    Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.