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

DAVE, NOOPUR; CETINER, UGUR; ARROYO, DANIEL; FONBUENA, JOSHUA; TIWARI, MEGNA; BARRERA, PATRICIA; LANDER, NOELIA; ANISHKIN, ANDRIY; SUKHAREV, SERGEI; JIMENEZ, VERONICA

eLife

Cambridge, UK : eLife Sciences Publications, Ltd., 2012

Lugar: Cambridge, UK ; Año: 2021 vol. 10

Abstract The causative agent of Chagas disease undergoes drastic morphological andbiochemical modifications as it passes between hosts and transitions from extracellular tointracellular stages. The osmotic and mechanical aspects of these cellular transformations are notunderstood. Here we identify and characterize a novel mechanosensitive channel in Trypanosomacruzi (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 vacuolecomplex in epimastigotes to the plasma membrane as the parasites develop into intracellularamastigotes. TcMscS knockout parasites show significant fitness defects, including increased cellvolume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity. Ourwork provides mechanistic insights into components supporting pathogen adaptation inside thehost, thus opening the exploration of mechanosensation as a prerequisite for protozoan infectivity.