A novel mechanosensitive channel controls osmoregulation, differentiation, and infectivity in 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 cha...

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Detalles Bibliográficos
Autores: Dave, Noopur, Cetiner, Ugur, Arroyo, Daniel, Fonbuena, Joshua, Tiwari, Megna, Barrera, Patricia Andrea, Lander, Noelia, Anishkin, Andriy, Sukharev, Sergei, Jimenez, Veronica
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/174639
Acceso en línea:http://hdl.handle.net/11336/174639
Access Level:acceso abierto
Palabra clave:TRYPANOSOMA CRUZI
MECHANOSENSATION
CRISPR-CAS9
INFECTIVITY
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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 Trypanosoma 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 for protozoan infectivity.