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The acidocalcisome Ca 2+ ‐ATPase ( TgA1 ) of Toxoplasma gondii is required for polyphosphate storage, intracellular calcium homeostasis and virulence
Author(s) -
Luo Shuhong,
Ruiz Felix A.,
Moreno Silvia N. J.
Publication year - 2005
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2004.04464.x
Subject(s) - biology , microneme , toxoplasma gondii , atpase , calcium , plasma membrane ca2+ atpase , virulence , complementation , secretion , extracellular , intracellular , microbiology and biotechnology , biochemistry , organelle , homeostasis , calcium in biology , mutant , enzyme , gene , medicine , apicomplexa , malaria , antibody , immunology , plasmodium falciparum
Summary A large proportion of intracellular Ca 2+ in Toxoplasma gondii tachyzoites is stored within acidocalcisomes. These organelles are characterized by their acidic nature and high calcium and polyphosphate (polyP) content. The activity of a Ca 2+ /H + ‐ATPase named Tg A1 may be important for the accumulation of Ca 2+ in these organelles. This enzyme belongs to a group of plasma membrane Ca 2+ ‐ATPase (PMCA) that lack a calmodulin‐binding domain and have vacuolar localization. To investigate the role of this enzyme, we have generated T. gondii mutants deficient in Tg A1 through gene disruption. Proliferation of these mutants decreased dramatically because of deficient cell invasion. In addition, these cells had reduced virulence in a mouse model. Biochemical analysis revealed that the cell polyP content was drastically reduced, and the basal calcium levels were increased and unstable. Microneme secretion under the conditions of stimulation by ionophores was altered. Complementation of null mutants with TgA1 restored most functions. In summary, these results establish a link between Tg A1, calcium homeostasis, polyP storage and virulence.