A novel mechanosensitive channel controls osmoregulation, differentiation and infectivity in Trypanosoma cruzi

  1. Noopur Dave
  2. Ugur Cetiner
  3. Daniel Arroyo
  4. Joshua Fonbuena
  5. Megna Tiwari
  6. Patricia Barrera
  7. Noelia Lander
  8. Andriy Anishkin
  9. Sergei Sukharev
  10. Veronica Jimenez  Is a corresponding author
  1. California State University Fullerton, United States
  2. University of Maryland, College Park, United States
  3. Facultad de Ciencias Exactas y Naturales, Instituto de Histologia y Embriologia IHEM-CONICET, Facultad de Medicina, Universidad Nacional de Cuyo, Argentina
  4. University of Cincinnati, United States
  5. University of Maryland, United States

Abstract

Trypanosoma cruzi, the causative agent of Chagas disease, undergoes drastic morphological and biochemical modifications as it passes between hosts and transitions from extracellular to intracellular stages. The osmotic and mechanical aspects of these cellular transformations are not understood. Here we identify and characterize a novel mechanosensitive channel in T. cruzi (TcMscS) belonging to the superfamily of small conductance mechanosensitive channels (MscS). TcMscS is activated by membrane tension and forms a large pore permeable to anions, cations, and small osmolytes. The channel changes its location from the contractile vacuole complex in epimastigotes to the plasma membrane as the parasites develop into intracellular amastigotes. TcMscS knockout parasites show significant fitness defects, including increased cell volume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity. Our work provides mechanistic insights into components supporting pathogen adaptation inside the host thus opening the exploration of mechanosensation as a prerequisite of protozoan infectivity.

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All data generated in this study are included in the manuscript, supporting files and source data files.

Article and author information

Author details

  1. Noopur Dave

    Biological Science, California State University Fullerton, Fullerton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1798-1824
  2. Ugur Cetiner

    Department Of Biology & Maryland Biophysics Program, University of Maryland, College Park, Hyattsville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5267-0749
  3. Daniel Arroyo

    Biological Science, California State University Fullerton, Fullerton, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joshua Fonbuena

    Biological Science, California State University Fullerton, Fullerton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Megna Tiwari

    Biological Science, California State University Fullerton, Fullerton, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Patricia Barrera

    Departamento de Biologia, Facultad de Ciencias Exactas y Naturales, Instituto de Histologia y Embriologia IHEM-CONICET, Facultad de Medicina, Universidad Nacional de Cuyo, Mendoza, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  7. Noelia Lander

    Biological Sciences, University of Cincinnati, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Andriy Anishkin

    Department of Biology, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sergei Sukharev

    Department of Biology, University of Maryland, College Park, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Veronica Jimenez

    Biological Science, California State University Fullerton, Fullerton, United States
    For correspondence
    vjimenezortiz@fullerton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0744-8137

Funding

National Institute of Allergy and Infectious Diseases (R15AI122153)

  • Veronica Jimenez

American Heart Association (16GRNT30280014)

  • Veronica Jimenez

National Institutes of Health (2T34GM008612-23)

  • Joshua Fonbuena

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

Reviewing Editor

  1. Christine Clayton, DKFZ-ZMBH Alliance, Germany

Version history

  1. Received: February 11, 2021
  2. Accepted: July 1, 2021
  3. Accepted Manuscript published: July 2, 2021 (version 1)
  4. Version of Record published: July 15, 2021 (version 2)

Copyright

© 2021, Dave 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. Noopur Dave
  2. Ugur Cetiner
  3. Daniel Arroyo
  4. Joshua Fonbuena
  5. Megna Tiwari
  6. Patricia Barrera
  7. Noelia Lander
  8. Andriy Anishkin
  9. Sergei Sukharev
  10. Veronica Jimenez
(2021)
A novel mechanosensitive channel controls osmoregulation, differentiation and infectivity in Trypanosoma cruzi
eLife 10:e67449.
https://doi.org/10.7554/eLife.67449

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https://doi.org/10.7554/eLife.67449