Trends in Parasitology
Volume 18, Issue 5, 1 May 2002, Pages 198-201
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Research update
Toxoplasma gondii tachyzoite–bradyzoite interconversion

https://doi.org/10.1016/S1471-4922(02)02248-1Get rights and content

Abstract

During infection in the intermediate host, Toxoplasma gondii undergoes stage conversion between the rapidly dividing tachyzoite that is responsible for acute toxoplasmosis and the slowly replicating, encysted bradyzoite stage. This process of tachyzoite–bradyzoite interconversion is central to the pathogenesis and longevity of infection. Recent research has identified several stage-specific genes and proteins. However, despite recent advances in the understanding of Toxoplasma cell biology, more research is necessary to elucidate the complex events occurring during tachyzoite–bradyzoite interconversion. Here, a brief summary of this process is provided and a new method to characterize gene expression during interconversion isintroduced.

Section snippets

Interconversion and disease pathogenesis

Initial infection and acute disease are characterized by the presence of fast-replicating tachyzoites. Around 10–14days post infection, tachyzoites differentiate into bradyzoites that replicate more slowly and form cysts in tissues throughout the body. Tissue cysts are long-lived and not associated with disease. However, in people with immunodeficiencies, such as AIDS or malignancies, rupture of tissue cysts and the transformation of bradyzoites to tachyzoites results in disease reactivation.

In vitro tachyzoite–bradyzoite differentiation

Whereas reports of cyst-like structures developing in tissue culture have existed since 1963 [1], it is only recently that reliable in vitro systems have been developed [2]. The most widely used invitro system involves growing the parasites in alkaline medium [2]. In common with other methods known to induce stage conversion, such as heat shock or acid conditions, this method appears to rely on stressing the parasite. Inhibitors of mitochondrial function and inducers of oxidative stress have

Differences between tachyzoites and bradyzoites

A fundamental difference between tachyzoites and bradyzoites is the resistance of bradyzoites to acid-pepsin digestion, although recent evidence suggests that oral infectivity in mice or acid-pepsin digestion as the sole criterion to distinguish between tachyzoites and bradyzoites cannot be relied on [7]. However, in vitro cultured cyst-like structures, obtained after six days of culture, have been demonstrated to contain acid-pepsin-resistant bradyzoites [8]. However, to accurately determine

New tool for interconversion analysis

Investigating the process of stage conversion necessitates the use of many techniques. Immunostaining and microscopy have been crucial in evaluating protein expression, whereas EST libraries and subtractive libraries have identified several interesting candidate genes. The development of a system for transfection of T. gondii has enabled gene replacement and the generation of stage-specific gene knockout parasites for evaluating the effect of individual genes during interconversion 17., 28..

Acknowledgements

This work was funded by the Wellcome Trust, NIH, USA RO1 AI-IMP44572 and the University of Strathclyde Research and Development Fund and Scottish Hospitals Endowments Research Trust. R.McL. is the Jules and Dorris Stein Research to Prevent Blindness Professor at the University of Chicago, USA.

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