The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell

  1. Jennifer E Dumaine
  2. Adam Sateriale
  3. Alexis R Gibson
  4. Amita G Reddy
  5. Jodi A Gullicksrud
  6. Emma N Hunter
  7. Joseph T Clark
  8. Boris Striepen  Is a corresponding author
  1. University of Pennsylvania, United States
  2. The Francis Crick Institute, United Kingdom
  3. University of Georgia, United States

Abstract

The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. Cryptosporidium invades enterocytes where it develops in a unique intracellular niche. Infected cells exhibit profound changes in morphology, physiology and transcriptional activity. How the parasite effects these changes is poorly understood. We explored the localization of highly polymorphic proteins and found members of the C. parvum MEDLE protein family to be translocated into the cytosol of infected cells. All intracellular life stages engage in this export, which occurs after completion of invasion. Mutational studies defined an N-terminal host-targeting motif and demonstrated proteolytic processing at a specific leucine residue. Direct expression of MEDLE2 in mammalian cells triggered an ER stress response, which was also observed during infection. Taken together, our studies reveal the presence of a Cryptosporidium secretion system capable of delivering parasite proteins into the infected enterocyte.

Data availability

The RNA sequencing dataset generated from the MEDLE2 transfection experiment has been deposited in GEO under accession number GSE174117. Source code and data files for this dataset were provided. Furthermore, numerical source data used for imaging quantification experiments in Figures 2 and 3 were provided.

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

Article and author information

Author details

  1. Jennifer E Dumaine

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Adam Sateriale

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexis R Gibson

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1078-4841
  4. Amita G Reddy

    Franklin College of Arts and Science, University of Georgia, Athens, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jodi A Gullicksrud

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Emma N Hunter

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Joseph T Clark

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Boris Striepen

    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    striepen@upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7426-432X

Funding

National Institute of Allergy and Infectious Diseases (R01AI127798)

  • Boris Striepen

National Institute of Allergy and Infectious Diseases (R01AI112427)

  • Boris Striepen

National Institute of Allergy and Infectious Diseases (T32AI007532)

  • Jennifer E Dumaine

National Institute of Allergy and Infectious Diseases (K99AI137442)

  • Adam Sateriale

National Institute of Allergy and Infectious Diseases (T32A1055400)

  • Jodi A Gullicksrud

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

Reviewing Editor

  1. Olivier Silvie, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, France

Ethics

Animal experimentation: All animals used in this study were handled and cared for in accordance with approved Institutional Animal Care and Use Committee protocols at the University of Georgia (protocol A2016 01-028-Y1-A4) and the University of Pennsylvania (protocol #806292).

Version history

  1. Received: May 17, 2021
  2. Preprint posted: June 4, 2021 (view preprint)
  3. Accepted: November 19, 2021
  4. Accepted Manuscript published: December 6, 2021 (version 1)
  5. Version of Record published: December 20, 2021 (version 2)

Copyright

© 2021, Dumaine 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. Jennifer E Dumaine
  2. Adam Sateriale
  3. Alexis R Gibson
  4. Amita G Reddy
  5. Jodi A Gullicksrud
  6. Emma N Hunter
  7. Joseph T Clark
  8. Boris Striepen
(2021)
The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell
eLife 10:e70451.
https://doi.org/10.7554/eLife.70451

Share this article

https://doi.org/10.7554/eLife.70451

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