An intestinally secreted host factor promotes microsporidia invasion of C. elegans

  1. Hala Tamim El Jarkass
  2. Calvin Mok
  3. Michael R Schertzberg
  4. Andrew G Fraser
  5. Emily R Troemel
  6. Aaron W Reinke  Is a corresponding author
  1. University of Toronto, Canada
  2. University of California, San Diego, United States

Abstract

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression of AAIM-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favoured in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild type animals. Together, this work demonstrates how microsporidia exploits a secreted protein to promote host invasion. Our results also suggest evolutionary trade-offs may exist to optimizing host defense against multiple classes of pathogens.

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All data generated during this study have been uploaded as source data files for each figure.

Article and author information

Author details

  1. Hala Tamim El Jarkass

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Calvin Mok

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael R Schertzberg

    The Donnelly Centre, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrew G Fraser

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9939-6014
  5. Emily R Troemel

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2422-0473
  6. Aaron W Reinke

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    For correspondence
    aaron.reinke@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7612-5342

Funding

Canadian Institutes of Health Research (400784)

  • Aaron W Reinke

Alfred P. Sloan Foundation (FG2019-12040)

  • Aaron W Reinke

National Institutes of Health (AG052622)

  • Emily R Troemel

National Institutes of Health (GM114139)

  • Emily R Troemel

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

Reviewing Editor

  1. Sebastian Lourido, Whitehead Institute for Biomedical Research, United States

Version history

  1. Received: July 23, 2021
  2. Preprint posted: December 13, 2021 (view preprint)
  3. Accepted: January 6, 2022
  4. Accepted Manuscript published: January 7, 2022 (version 1)
  5. Version of Record published: February 1, 2022 (version 2)
  6. Version of Record updated: February 11, 2022 (version 3)
  7. Version of Record updated: March 25, 2022 (version 4)

Copyright

© 2022, Tamim El Jarkass 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. Hala Tamim El Jarkass
  2. Calvin Mok
  3. Michael R Schertzberg
  4. Andrew G Fraser
  5. Emily R Troemel
  6. Aaron W Reinke
(2022)
An intestinally secreted host factor promotes microsporidia invasion of C. elegans
eLife 11:e72458.
https://doi.org/10.7554/eLife.72458

Share this article

https://doi.org/10.7554/eLife.72458

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