A ubiquitous intracellular parasite: The cellular biology of Toxoplasma gondii

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Abstract

Toxoplasma gondii shares many features with other apicomplexan parasites but is unusual in its extremely broad host and tissue specificity. The parasite exhibits typical ‘zoite’ morphology, its highly polar structure being dictated by the complex cytoskeleton. Molecules on the surface of the zoite are prime candidates for interaction with the host cell and in vitro assays have implicated 2 of the 5 tachyzoite surface molecules in invasion: SAG1 as a ligand mediating host cell invasion, and SAG2 in enabling reorientation prior to invasion. The functional roles of other molecules, secreted from internal organelles during invasion and intracellular development, are also becoming clear through immuno-EM and biochemical studies, and from sequence data. Molecules from the rhoptries including the penetration enhancing factor ROP1 are secreted at the point of invasion and are integral to the newly formed parasitophorous vacuole membrane. Release of the dense granule molecules GRA 1–6, appears to be calcium regulated and occurs within 10 min of invasion leading to formation of the tubular membranous network and stabilization of the vacuole. The interaction between Toxoplasma and the host cell is stage specific. The tachyzoite divides rapidly and synchronously forming rosettes and causing host cell lysis, while the bradyzoite exhibits slow asynchronous division secreting a granular matrix and becoming enclosed within a cyst wall. This altered phenotype is a reflection of changes in gene expression. Bradyzoite specific molecules are found internally, on the parasite surface, and in the cyst matrix while important tachyzoite proteins such as SAG1 and SAG2 are downregulated. Differentiation between the 2 stages is reversible and is influenced by immunomodulatory agents. However a strong genetic element is involved and it is notable that virulent strains show a very low frequency of cyst production.

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