1. Microbiology and Infectious Disease
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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
Research Article
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Cite this article as: eLife 2022;11:e72458 doi: 10.7554/eLife.72458

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

Publication history

  1. Received: July 23, 2021
  2. Accepted: January 6, 2022
  3. Accepted Manuscript published: January 7, 2022 (version 1)

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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Further reading

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    Conclusions: The finding that SARS-CoV-2 mRNA vaccination resulted in binding to additional epitopes beyond what was seen after infection suggests protection could vary depending on the route of exposure to Spike antigen. The relatively conserved escape pathways to vaccine-induced antibodies relative to infection-induced antibodies suggests that if escape variants emerge, they may be readily selected for across vaccinated individuals. Given that the majority of people will be first exposed to Spike via vaccination and not infection, this work has implications for predicting the selection of immune escape variants at a population level.

    Funding: This work was supported by NIH grants AI138709 (PI Overbaugh) and AI146028 (PI Matsen). Julie Overbaugh received support as the Endowed Chair for Graduate Education (FHCRC). The research of Frederick Matsen was supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute and the Simons Foundation. Scientific Computing Infrastructure at Fred Hutch was funded by ORIP grant S10OD028685.

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