The determinants regulating Toxoplasma gondii bradyzoite development

Abstract

Toxoplasma gondii is an obligate intracellular zoonotic pathogen capable of infecting almost all cells of warm-blooded vertebrates. In intermediate hosts, this parasite reproduces asexually in two forms, the tachyzoite form during acute infection that proliferates rapidly and the bradyzoite form during chronic infection that grows slowly. Depending on the growth condition, the two forms can interconvert. The conversion of tachyzoites to bradyzoites is critical for T. gondii transmission, and the reactivation of persistent bradyzoites in intermediate hosts may lead to symptomatic toxoplasmosis. However, the mechanisms that control bradyzoite differentiation have not been well studied. Here, we review recent advances in the study of bradyzoite biology and stage conversion, aiming to highlight the determinants associated with bradyzoite development and provide insights to design better strategies for controlling toxoplasmosis.

Functional analyses of Toxoplasma gondii dihydroorotase reveal a promising anti‐parasitic target

“…However, our study did not compare the UMP levels of different strains due to a slower growth rate of bradyzoites upon DHO deletion. Considering unique metabolic characteristics of bradyzoites including stage specific expression of catalytic enzymes in the glycolysis and gluconeogenesis pathways, and the accumulation of abundant amylopectin granules, 5,48 a combination of carbon metabolism and the biosynthesis of pyrimidine is likely to design better strategies against chronic toxoplasmosis. Additionally, the distinctive cyst wall is highly resistant to most of anti‐ T. gondii drugs and consequently no clinical treatment is available for tissue cyst 49 .…”

“…Tachyzoites can differentiate into semi-dormant bradyzoites in immunocompetent hosts, but the reactivation of persistent bradyzoites in HIV-infected individuals and other immunocompromised hosts can lead to symptomatic toxoplasmosis. 4,5 For decades, the inhibitors targeting folate biosynthesis pathway of T. gondii are effective in treating acute toxoplasmosis. But due to the side effects and the inability to eradicate the chronic infection, these drugs are far from ideal.…”

“…In intermediate hosts, T. gondii propagates asexually in a rapidly dividing tachyzoite form and a slowly growing bradyzoite form, the two forms can interconvert based on the growth condition. Tachyzoites can differentiate into semi‐dormant bradyzoites in immunocompetent hosts, but the reactivation of persistent bradyzoites in HIV‐infected individuals and other immunocompromised hosts can lead to symptomatic toxoplasmosis 4,5 . For decades, the inhibitors targeting folate biosynthesis pathway of T. gondii are effective in treating acute toxoplasmosis.…”

A bioinformatic approach for the prediction and functional classification ofToxoplasma gondiilong non-coding RNAs

“…Carbohydrate metabolic processes are the most enriched BP and oxidoreductase activity MF. A close inspection over this cluster led us to find that it is composed of transcripts that codify for relevant proteins in the bradyzoite stage like BAG1, ENO1, LDH2, CST7, MAG2 and PMA1 [29][30][31][32] . In fact, we observed the presence of BFD2, recently documented as a RNA binding protein that regulates BFD1, a key regulator for bradyzoite development 33 .…”

Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii

“…Due to the wide range of intermediate hosts, T. gondii has the metabolic flexibility to adapt to different host environments and physiological changes. In intermediate hosts, T. gondii proliferates asexually in two forms, including tachyzoites causing acute infection with rapid proliferation, and slow-growing bradyzoites causing chronic infection [ 3 ]. Upon invasion of host cells, the parasite relies on the substantial uptake of nutrients from the host to satisfy its nutritional requirements for rapid proliferation, including lipids, proteins, and various metal ions [ 4 , 5 ].…”