Abstract

The apicomplexan zoonotic parasite Toxoplasma gondii has three infective stages: sporozoites in sporulated oocysts, which are shed in unsporulated form into the environment by infected felids; tissue cysts containing bradyzoites, and fast replicating tachyzoites that are responsible for acute toxoplasmosis. The contribution of oocysts to infections in both humans and animals is understudied despite being highly relevant. Only a few diagnostic antigens have been described to be capable of discriminating which parasite stage has caused an infection. Here we provide an extensive overview of the antigens and serological assays used to detect oocyst-driven infections in humans and animals according to the literature. In addition, we critically discuss the possibility to exploit the increasing knowledge of the T. gondii genome and the various ‘omics datasets available, by applying predictive algorithms, for the identification of new oocyst-specific proteins for diagnostic purposes. Finally, we propose a workflow for how such antigens and assays based on them should be evaluated to ensure reproducible and robust results.

Highlights

  • The substantial infection rates seen in herbivores would support the high infectivity of the oocyst stage for other animals as well [29,30], consistent with the hypothesis that “T. gondii is biologically adapted to transmission by carnivorism in cats and by fecal–oral route in herbivores” [28]

  • It has been reasonable to propose that proteins expressed exclusively by T. gondii oocysts may help to identify the early phase of an oocyst-driven infection [62–64]

  • MW: molecular weight; Ref.: reference; N: natural infection; E: experimental infection; No: number; F: female; M: male; TZ: tachyzoites; TC: tissue cysts; Oo: Oocysts; WB: Western blot; rec: recombinant; w: weeks; d: days; na: no data available; dpi: days post-infection; +: seropositive; -: unknown. * Assays based on recombinant proteins. ** Authors claimed that these animals could possibly be infected with oocysts; Animal breed or strain were unknown in all studies. *** 15 T. gondii tachyzoite-positive porcine sera did not recognize OWP8 by WB

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Summary

A Quick Tour through the Life Cycle of Toxoplasma gondii

The apicomplexan protozoan Toxoplasma gondii is a highly successful cosmopolitan intracellular parasite of the Sarcocystidae family, which can cause a range of disease manifestations in humans and animals [1]. Toxoplasma gondii can be transmitted by three different developmental stages (infection routes): tachyzoites (congenital), bradyzoites within tissue cysts (meat-borne pathway), and sporozoites within sporulated oocysts (environmental pathway). T. gondii has been identified as a cause of reproductive disorders in sows and an increasing number of studies have reported outbreaks of clinical toxoplasmosis in fattening pigs [24,25]. Experimental data have shown that ingestion of tissue cysts is the most efficient transmission route for cats whilst for intermediate hosts (mice, rats, small ruminants, and pigs) this seems to be infection by oocysts [26–28]. The substantial infection rates seen in herbivores would support the high infectivity of the oocyst stage for other animals as well [29,30], consistent with the hypothesis that “T. gondii is biologically adapted to transmission by carnivorism in cats and by fecal–oral route in herbivores” [28]. Waterborne outbreaks have been easier to identify given the large number of people affected [33,40,44,45]

The Challenge of Differentiating between Meat-Borne and Oocyst-Driven
Investigating the Route of Infection—What Assays Are Available So Far?
Oocyst Wall Proteins
Results
What Makes a Protein a Good Antigen?
In Silico Prediction of the Surfaceome—Illustrating the Limits
Vennthe diagram illustrating
Statistical was performed with thedata
Genome-Wide Prediction of Linear B-Cell Epitopes
Conclusions
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