Toxoplasma gondii Tissue Cyst: Cyst Wall Incorporation Activity and Matrix Cytoskeleton Proteins Paving the Way to Nutrient Acquisition

Acquarone, Mariana; Ferreira-da-Silva, Marialice da Fonseca; Guimarães, Erick Vaz; Barbosa, Helene Santos

doi:10.5772/intechopen.68202

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…Protein folding prediction based on the C terminus of MAG2 revealed alpha helices and coiled coils (30,31), which suggests that MAG2 may have membrane associations (32). Finally, the central repeating domains of MAG2 share some homology with the repeating units of Futsch, a Drosophila microtubuleassociated protein (33), which suggests that MAG2 may be interacting with filamentous structures within the matrix (12,34).…”

Section: Discussionmentioning

confidence: 99%

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

Mayoral

Yakubu

et al. 2020

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Toxoplasma gondii causes a chronic infection that affects a significant portion of the world's population, and this latent infection is the source of reactivation of toxoplasmosis. An attribute of the slowly growing bradyzoite stage of the parasite is the formation of a cyst within infected cells, allowing the parasite to escape the host's immune response. In this study, a new bradyzoite cyst matrix antigen (MAG) was identified through a hybridoma library screen. This cyst matrix antigen, matrix antigen 2 (MAG2), contains 14 tandem repeats consisting of acidic, basic, and proline residues. Immunoblotting revealed that MAG2 migrates at a level higher than its predicted molecular weight, and computational analysis showed that the structure of MAG2 is highly disordered. Cell fractionation studies indicated that MAG2 was associated with both insoluble and soluble cyst matrix material, suggesting that it interacts with the intracyst network (ICN). Examination of the kinetics of MAG2 within the cyst matrix using fluorescence recovery after photobleaching (FRAP) demonstrated that MAG2 does not readily diffuse within the cyst matrix. Kinetic studies of MAG1 demonstrated that this protein has different diffusion kinetics in tachyzoite and bradyzoite vacuoles and that its mobility is not altered in the absence of MAG2. In addition, deletion of MAG2 does not influence growth, cystogenesis, or cyst morphology. IMPORTANCE This report expands on the list of characterized Toxoplasma gondii cyst matrix proteins. Using fluorescence recovery after photobleaching (FRAP), we have shown that matrix proteins within the cyst matrix are not mainly in a mobile state, providing further evidence of how proteins behave within the cyst matrix. Understanding the proteins expressed during the bradyzoite stage of the parasite reveals how the parasite functions during chronic infection. KEYWORDS latency, monoclonal antibody screen, intravacuolar network, MAG1, MAG2, Toxoplasma gondii, bradyzoite, cyst matrix, fluorescence recovery after photobleaching (FRAP) E xposure to contaminated food containing bradyzoites, which represent the latent stage of Toxoplasma gondii, or to oocysts containing sporozoites, which represent the sexual stage of the parasite, results in the transmission of this parasite (1). In the case of pregnant mothers, first-time exposure may lead to complications within the unborn fetus (2). While the levels of seroprevalence of T. gondii differ from country to country (3), it is estimated that 30% to 40% of the human population is latently infected with this parasite. There is currently no cure for this infection in the latent stage, and it is believed that this organism can persist for life in its hosts. The persistence of the infection is due to the ability of the parasite to differentiate from tachyzoites, representing the quickly proliferating stage, into bradyzoites, which can remain dormant within cysts for many years. When the host's immune system is weakened, the parasite FIG 2 20C3 MAb recognizes MAG2, a disordered 218-...

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Section: Discussionmentioning

confidence: 99%

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

Mayoral

Yakubu

et al. 2020

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“…A recent study has shown that cysts are not in a stationary state, but in rather dynamic equilibrium. A subset of bradyzoites within cysts are actively dividing (Sinai et al 2016) and the cyst membrane has been demonstrated to rapidly endocytose nutrients (Acquarone et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a SRS13: a new cyst wall mucin-like domain containing protein

Tomita

Weiss

2018

Parasitol Res

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Toxoplasma gondii, an obligate intracellular apicomplexan, causes latent infection in about one third of the human population. During latent infection, T. gondii bradyzoites are found within cysts, a modified parasitophorous vacuole. This parasite has a large family of SRS (surface antigen-1 related sequence) proteins which are reported to be involved in attachment of these organisms to their mammalian host cells and in immune subversion during latent infection. We have identified a novel mucin domain containing SRS protein, using a glycoepitope-specific antibody, which recognizes the cyst wall. SRS13 has two SRS domains and between these domains is a threonine-rich tandem repeat mucin-like domain that is similar to the mucin-like domain seen in another cyst wall specific SRS protein CST1 (SRS44). SRS13 is upregulated in bradyzoites and O-GalNAc glycosylated by ppGalNAc-T2 and T3. Similar to the cyst wall protein CST1, SRS13 localizes to the cyst wall, but unlike CST1, SRS13 is dispensable for normal cyst wall formation. Together, these findings elucidate the role of a second SRS mucin domain protein, SRS13, in bradyzoite biology and expands the previously reported functions of the SRS protein family.

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“…The vesicles, elongated tubules between bradyzoites, and filamentous material observed in the cyst matrix may thus reflect a complex trafficking network that could be used for nutrient acquisition [37]. As the cyst wall seems to be permeable to molecules which are 10 kDa or less [37], it is likely parasites within the cysts have access to nutrients from the cytoplasm of the host [97]. Finally, as mentioned in part 3, the latent tissue cysts are supposed to largely evade the immune response, although the part played by the cyst wall in limiting the interaction of the bradyzoites with the components of the immune response is not yet elucidated.…”

Section: Interfering With the Biogenesis Or The Integrity Of The Cyst Wallmentioning

confidence: 99%

The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis

2020

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Toxoplasma gondii is a ubiquitous parasitic protist found in a wide variety of hosts, including a large proportion of the human population. Beyond an acute phase which is generally self-limited in immunocompetent individuals, the ability of the parasite to persist as a dormant stage, called bradyzoite, is an important aspect of toxoplasmosis. Not only is this stage not eliminated by current treatments, but it can also reactivate in immunocompromised hosts, leading to a potentially fatal outcome. Yet, despite its critical role in the pathology, the bradyzoite stage is relatively understudied. One main explanation is that it is a considerably challenging model, which essentially has to be derived from in vivo sources. However, recent progress on genetic manipulation and in vitro differentiation models now offers interesting perspectives for tackling key biological questions related to this particularly important developmental stage.

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Toxoplasma gondii Tissue Cyst: Cyst Wall Incorporation Activity and Matrix Cytoskeleton Proteins Paving the Way to Nutrient Acquisition

Cited by 5 publications

References 39 publications

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

Characterization of a SRS13: a new cyst wall mucin-like domain containing protein

The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis

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