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.
Trypanosoma cruzi, the causative agent of Chagas disease undergoes drastic cellular morphological and biochemical changes as it passes from extracellular epimastigote and trypomastigote forms, to intracellular/tissue non-motile stage. Here we describe and characterize a mechanosensitive channel in T. cruzi (TcMscS), which is homologous to bacterial MscS. TcMscS is present in the contractile vacuole of extracellular stages but redistributes to the plasma membrane in intracellular amastigotes. The heterologously expressed TcMscS is activated by membrane tension (12 mN/m) forming a large 0.4 nS pore permeable to both anions and cations and possibly small osmolytes. The TcMscS knockdown and knockout T. cruzi strains, generated by CRISPR-Cas9 gene targeting, show slower growth in intracellular and extracellular stages, inability to robustly regulate volume and a dramatically decreased infectivity. Our study shows that the tension-driven mechanosensitive channel fulfills multiple roles in different stages of T. cruzi life cycle and is essential for infectivity.
SignificanceProtozoan parasites transmited by insect vectors have the ability to infect a variety of mammalian host, completing their development in various environments. Their capacity to detect and respond to changes in external conditions is key for their survival but the mechanisms involved in sensing are poorly described. Mechanosensation plays an important role in regulating pathogenicity and cell development. Here, we have identified and characterized a mechanosensitive channel required for osmotic regulation in Trypanosoma cruzi. The ablation of the gene renders parasites with impaired replication and severe infectivity defects. Our work is providing new elements to understand host-pathogen interaction and cellular homeostasis.
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