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New Strategies for an Old Problem: Calcium Regulation in the Apicomplexan parasite, Toxoplasma gondii
Author(s) -
Pace Douglas,
Moreno Silvia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.844.6
Subject(s) - toxoplasma gondii , biology , extracellular , calcium , intracellular parasite , virulence , calcium in biology , microbiology and biotechnology , intracellular , calcium signaling , parasite hosting , calcium channel , gene , biochemistry , genetics , chemistry , organic chemistry , world wide web , computer science , antibody
The complex relationships between protozoan intracellular parasites and their mammalian hosts suggests that ion regulatory pathways must play several defining roles in virulence. Calcium regulation is of particular importance because of the vast number of processes it regulates both within the host cell and parasite. The Apicomplexan parasite, Toxoplasma gondii , is a highly successful intracellular parasite capable of invading any nucleated mammalian cell. Genomic evidence of ion channels is scarce due to the high level of sequence divergence in protozoan parasites. While the importance of intracellular calcium is established for this parasite, the role of extracellular calcium and its entry pathways is unknown. Using the fluorescent, cell permeable calcium indicator, Fura2‐AM, we show that tachyzoites of T. gondii possess distinct pathways of extracellular calcium entry linked to the activity of an L‐type Ca 2+ channel. Importantly, several aspects of parasite virulence showed a strong positive association with extracellular calcium entry. To further understand real‐time calcium responses genetically encoded calcium indicators (GECIs) were developed for T. gondii . These newly developed GECIs have provided the first direct, real‐time observations of simultaneous calcium flux in parasites and host cells during invasion and egress.These new approaches and tools will be critical in understanding the coordinated regulation of calcium in T. gondii , as well as other Apicomplexans. These tools will enable a platform for identifying ion regulatory genes for drug targeting and treating Apicomplexan infections in a wide range of mammals including humans. Support: NIH: R01AI096836, T32 training grant AI‐60546