Observations on bradyzoite biology

Abstract

Tachyzoites of the Apicomplexan Toxoplasma gondii cause acute infection, disseminate widely in their host, and eventually differentiate into a latent encysted form called bradyzoites that are found within tissue cysts. During latent infection, whenever transformation to tachyzoites occurs, any tachyzoites that develop are removed by the immune system. In contrast, cysts containing bradyzoites are sequestered from the immune system. In the absence of an effective immune response released organisms that differentiate into tachyzoites cause acute infection. Tissue cysts, therefore, serve as a reservoir for the reactivation of toxoplasmosis when the host becomes immunocompromised by conditions such as HIV infection, organ transplantation, or due to the impaired immune response that occurs when pathogens are acquired in utero. While tachyzoites and bradyzoites are well defined morphologically, there is no clear consensus on how interconversion occurs or what exact signal(s) mediate this transformation. Advances in research methods have facilitated studies on T. gondii bradyzoites providing important new insights into the biology of latent infection.

Succinylated Wheat Germ Agglutinin Colocalizes with the Toxoplasma gondii Cyst Wall Glycoprotein CST1

“…These results support the hypothesis that N-acetylglucosamine-modified molecules that bind to s-WGA and colocalize with CST1 play a role in the development and structure of the cyst wall. Genetic deletion of CST1 results in a leaky-cyst phenotype marked by the escape of cyst matrix proteins from the cyst (53), which supports the previously proposed model that O-linked N-acetylgalactosamine glycosylation regulates the permeability of the cyst wall. It is tempting to speculate that N-acetylgalactosaminemodified CST1-and N-acetylglucosamine-modified s-WGA binding molecules together establish permeability conduits in the cyst wall that allow the permeation of small essential host molecules such as glucose (57) and nucleotide sugars (27) and, perhaps, vesicular traffic.…”

“…O-linked glycosylation of CST1 is essential for establishing cyst wall thickness and cyst stability (19,23). N-Acetylgalactosamine-modified CST1 has been hypothesized to be a key cyst wall scaffolding molecule that interacts with other cyst wall proteins to provide a walled structure that supports cyst stability (13,53). Our results show that the cyst wallglycosylated molecule(s) that binds s-WGA colocalized with CST1 in the cyst wall.…”

Toxoplasma gondii Parasitophorous Vacuole Membrane-Associated Dense Granule Proteins Orchestrate Chronic Infection and GRA12 Underpins Resistance to Host Gamma Interferon

“…The presence of cysts in the central nervous system characterizes the chronic stage of Toxoplasma infection (6, 10, 11). A limiting membrane termed the cyst membrane surrounds the cyst wall (7, 8), and while this cyst membrane is hypothesized to arise from the modified PVM (7, 8, 76), the fate and trafficking of PVM and IVN membrane proteins during differentiation and cyst development still remain to be investigated. Similar to the IVN membranes present in acute-stage tachyzoite PVs, mature cysts contain membrane tubules that, within an intracyst matrix, link the bradyzoites to each other and to the cyst wall and, possibly, to the cyst membrane (7).…”

Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii

“…If the progression from replicating H. hammondi zoite to tissue cyst is as predictable in vivo as it is in vitro (which is unknown but likely given that even IFN-γ knockout mice survive infection with H. hammondi ; [ Dubey and Sreekumar, 2003 ]), and H. hammondi has non- or less-functional orthologs of genes like TgIST ( Hakimi et al, 2017 ; Olias et al, 2016 ; Gay et al, 2016 ), this may prevent the fixation of any polymorphisms in the population that might result in the suppression of spontaneous bradyzoite conversion. Given that bradyzoites induce less inflammation ( Kim et al, 2007 ) and are protected from immune assaults by the tissue cyst wall ( Tu et al, 2017 ; Alday and Doggett, 2017 ), the timing of these events may be under very strong selective pressure in H. hammondi . It will be interesting to see how the developmental dynamics of H. hammondi in vivo are timed with that of the intermediate host immune response, particularly in rodents ( Sheffield et al, 1976 ; Frenkel and Dubey, 1975 ; Mason, 1978 ), since this may have directly impacted the timing of cyst formation during the evolution of this parasite.…”