The role of potassium and host calcium signaling in Toxoplasma gondii egress

Toxoplasma gondii is an obligate intracellular parasite and replicates inside a parasitophorous vacuole (PV) within the host cell. The membrane of the PV (PVM) contains pores that permits for equilibration of ions and small molecules between the host cytosol and the PV lumen. Ca²⁺ signaling is universal and both T. gondii and its mammalian host cell utilize Ca²⁺ signals to stimulate diverse cellular functions. Egress of T. gondii from host cells is an essential step for the infection cycle of T. gondii, and a cytosolic Ca²⁺ increase initiates a Ca²⁺ signaling cascade that culminates in the stimulation of motility and egress. In this work we demonstrate that intracellular T. gondii tachyzoites are able to take up Ca²⁺ from the host cytoplasm during host cell signaling events. Both intracellular and extracellular Ca²⁺ sources are important in reaching a threshold of parasite cytosolic Ca²⁺ needed for successful egress. Two peaks of Ca²⁺ were observed in egressing single parasites with the second peak resulting from Ca²⁺ entry. We patched infected host cells to allow the delivery of precise concentrations of Ca²⁺ for the stimulation of motility and egress. Using this approach of patching infected host cells, allowed us to determine that increasing the host cytosolic Ca²⁺ to a specific concentration can trigger egress, which is further accelerated by diminishing the concentration of potassium (K⁺).

Stephen A Vella, Christina A Moore, Zhu-Hong Li, Miryam A Hortua Triana, Evgeniy Potapenko, Silvia N J Moreno. Cell Calcium. 2021 Jan 19;94:102337. doi: 10.1016/j.ceca.2020.102337