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A vacuolar‐ H + ‐pyrophosphatase ( TgVP 1) is required for microneme secretion, host cell invasion, and extracellular survival of T oxoplasma gondii
Author(s) -
Liu Jing,
Pace Douglas,
Dou Zhicheng,
King Thayer P.,
Guidot Daniel,
Li ZhuHong,
Carruthers Vern B.,
Moreno Silvia N. J.
Publication year - 2014
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/mmi.12685
Subject(s) - microneme , biology , toxoplasma gondii , secretion , microbiology and biotechnology , extracellular , bafilomycin , mutant , vacuole , biochemistry , cytoplasm , apicomplexa , immunology , apoptosis , autophagy , malaria , gene , antibody , plasmodium falciparum
Summary The vacuolar proton pyrophosphatase ( H + ‐ PP ase) of T oxoplasma gondii ( TgVP 1), a membrane proton pump, localizes to acidocalcisomes and a novel lysosome‐like compartment termed plant‐like vacuole ( PLV ) or vacuolar compartment ( VAC ). We report the characterization of a T . gondii null mutant for the TgVP1 gene. Propagation of these mutants decreased significantly because of deficient attachment and invasion of host cells, which correlated with deficient microneme secretion. Processing of cathepsin L ( CPL ) in these mutants was deficient only when the parasites were incubated in the presence of low concentrations of the vacuolar H + ‐ ATP ase ( V ‐ H + ‐ ATP ase) inhibitor bafilomycin A 1 , suggesting that either TgVP 1 or the T . gondii V ‐ H + ‐ ATP ase ( TgVATP ase) are sufficient to support CPL processing. The lack of TgVP 1 did not affect processing of micronemal proteins, indicating that it does not contribute to pro MIC maturations. The TgVP1 null mutants were more sensitive to extracellular conditions and were less virulent in mice. We demonstrate that T . gondii tachyzoites possess regulatory volume decrease capability during hypo‐osmotic stress and this ability is impaired in TgVP1 null mutants implicating TgVP 1 in osmoregulation. We hypothesize that osmoregulation is needed for host cell invasion and that TgVP 1 plays a role during the normal lytic cycle of T . gondii .