A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasites

Abstract

Plasma membrane-located transport proteins are key adaptations for obligate intracellular Microsporidia parasites, because they can use them to steal host metabolites the parasites need to grow and replicate. However, despite their importance, the functions and substrate specificities of most Microsporidia transporters are unknown. Here we provide functional data for a family of transporters conserved in all microsporidian genomes and also in the genomes of related endoparasites. The universal retention among otherwise highly reduced genomes indicates an important role for these transporters for intracellular parasites. Using Trachipleistophora hominis, a Microsporidia isolated from an HIV/AIDS patient, as our experimental model, we show that the proteins are ATP and GTP transporters located on the surface of parasites during their intracellular growth and replication. Our work identifies a new route for the acquisition of essential energy and nucleotides for a major group of intracellular parasites that infect most animal species including humans.

Data availability

New sequences data were submitted to GenBank:1) RNA-Seq data: BioProject PRJNA278775 with the BioSample accession numbers SAMN11265032-SAMN11265043 (one accession for each of the two samples per time point post infection).2) The new native PCR cloned gene sequences have the following GenBank accession numbers: ThMFS2_native: MH824667; ThMFS3_native: MH8246683) Codon-optimized genes for expression in E. coli have the following GenBank accession numbers: ThMFS1_synthetic: MH824663; ThMFS2_synthetic: MH824664; ThMFS3_synthetic: MH824665; ThMFS4_synthetic: MH824666These are all listed in the Materials and Methods section, see Key Resources Table.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Peter Major

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Kacper M Sendra

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Paul Dean

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Tom A Williams

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew K Watson

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. David T Thwaites

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. T Martin Embley

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    For correspondence
    martin.embley@ncl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  8. Robert P Hirt

    Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
    For correspondence
    robert.hirt@ncl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3760-9958

Funding

Wellcome (089803/Z/09/Z)

  • T Martin Embley

European Research Council Advanced Investigator Program (ERC 2010-268701)

  • T Martin Embley

Biotechnology and Biological Sciences Research Council (PhD studentship)

  • Andrew K Watson

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

Reviewing Editor

  1. Emily Troemel, University of California, San Diego, United States

Publication history

  1. Received: March 20, 2019
  2. Accepted: July 23, 2019
  3. Accepted Manuscript published: July 29, 2019 (version 1)
  4. Version of Record published: August 19, 2019 (version 2)

Copyright

© 2019, Major 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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  1. Peter Major
  2. Kacper M Sendra
  3. Paul Dean
  4. Tom A Williams
  5. Andrew K Watson
  6. David T Thwaites
  7. T Martin Embley
  8. Robert P Hirt
(2019)
A new family of cell surface located purine transporters in Microsporidia and related fungal endoparasites
eLife 8:e47037.
https://doi.org/10.7554/eLife.47037

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