A novel mechanosensitive channel controls osmoregulation, differentiation and infectivity in Trypanosoma cruzi
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.
Data availability
All data generated in this study are included in the manuscript, supporting files and source data files.
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Author details
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
- Christine Clayton, DKFZ-ZMBH Alliance, Germany
Publication history
- Received: February 11, 2021
- Accepted: July 1, 2021
- Accepted Manuscript published: July 2, 2021 (version 1)
- 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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