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.

A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission

“…Membrane stress may also result from parasite attachment to insect host tissue surfaces or cell-cell contacts in highly confined space, as observed for swarming P. aeruginosa 77 . As some trypanosome ACs seem to be activated by calcium in vivo [57][58][59][60] , the report of a membrane tension-mediated opening of a mechanosensitive ion channel in T. cruzi 78 may merit follow-up in this context.…”

The Kinetoplastid-Specific Protein TcCAL1 Plays Different Roles During In Vitro Differentiation and Host-Cell Invasion in Trypanosoma cruzi

“…Along with a change in the morphology and the metabolic state, an abrupt but transitional increase in the cytosolic Ca 2+ occurs during T. cruzi metacyclogenesis ( Lammel et al., 1996 ; Hashimoto et al., 2016 ; Gonçalves et al., 2018 ). Several Ca 2+ - or Ca 2+ -activated channels involved in metacyclogenesis and other processes have been identified in the parasite ( Furuya et al., 2001 ; Ramakrishnan and Docampo, 2018 ; Chiurillo et al., 2019 ; Dave et al., 2021 ). Meanwhile, few Ca 2+ -binding or -regulated proteins have been characterized so far ( Belaunzarán et al., 2009 ; Hamedi et al., 2015 ; Lander et al., 2018 ), and three proteins involved in calcium homeostasis have been shown to play a role in metacyclogenesis: MICU1 and MICU2 ( Bertolini et al., 2019 ) and Letm1 ( Dos Santos et al., 2021 ).…”

“…Regarding this, the main intracellular reservoirs studied to date for Ca 2+ storage and mobilization are the acidocalcisomes, the endoplasmic reticulum and the mitochondria ( Lu et al., 1998 ; Maeda et al., 2012 ; Chiurillo et al., 2020 ). Nearly a dozen Ca 2+ transport channels have been identified and/or characterized in these organelles, as well as in plasma or flagellar membranes ( Furuya et al., 2001 ; Hamedi et al., 2015 ; Ramakrishnan and Docampo, 2018 ; Chiurillo et al., 2019 ; Dave et al., 2021 ), which handle the mobilization, flux, and extrusion of Ca 2+ ions among the different compartments and the extracellular environment. The differences in structure, location, and regulation found in some of these channels in comparison to those present in mammalian cells, in addition to their relevance in parasite physiology, make these channels an attractive target for therapeutic treatment ( Benaim et al., 2020 ).…”

The old and the new about the contractile vacuole of Trypanosoma cruzi

“…In Trypanosoma cruzi , most of the structural characterization of the CVC has been carried out in the epimastigote form but there is evidence of its presence in amastigotes (Girard‐Dias et al, 2012) and trypomastigotes (Dave et al, 2021; Niyogi & Docampo, 2015). The parasites show a single central vacuole or bladder located close to the flagellar pocket, surrounded by a network of interconnected vesicles and tubules that form the spongiome (Figure 2A–C).…”