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

ABSTRACTTheToxoplasma gondiibradyzoite is essential to establish persistent infection, yet little is known about what factors this developmental form secretes to establish the cyst or interact with its host cell. To identify candidate bradyzoite-secreted effectors, the transcriptomes ofin vitrotachyzoites 2 days postinfection,in vitrobradyzoites 4 days postinfection, andin vivobradyzoites 21 days postinfection were interrogated by microarray, and the program SignalP was used to identify signal peptides indicating secretion. One hundred two putative bradyzoite-secreted effectors were identified by this approach. Two candidates, bradyzoite pseudokinase 1 and microneme adhesive repeat domain-containing protein 4, were chosen for further investigation and confirmed to be induced and secreted by bradyzoitesin vitroandin vivo. Thus, we report the first analysis of the transcriptomes ofin vitroandin vivobradyzoites and identify two new protein components of theToxoplasmatissue cyst wall.

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Anionic sites on Toxoplasma gondii tissue cyst wall: Expression, uptake and characterization

Micron ◽

10.1016/j.micron.2006.09.002 ◽

2007 ◽

Vol 38 (6) ◽

pp. 651-658 ◽

Cited By ~ 6

Author(s):

Erick Vaz Guimarães ◽

Mariana Acquarone ◽

Laís de Carvalho ◽

Helene Santos Barbosa

Keyword(s):

Toxoplasma Gondii ◽

Cyst Wall ◽

Tissue Cyst ◽

Anionic Sites

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Faculty Opinions recommendation of The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718226646.793492471 ◽

2014 ◽

Author(s):

Frank Seeber

Keyword(s):

Toxoplasma Gondii ◽

Cyst Wall

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Evolution of IgG antibody response against Toxoplasma gondii tissue cyst in acute and chronic human infections

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651998000200003 ◽

1998 ◽

Vol 40 (2) ◽

pp. 77-84 ◽

Cited By ~ 2

Author(s):

Margarita VILLAVEDRA ◽

Hernán CAROL ◽

Alberto NIETO

Keyword(s):

Toxoplasma Gondii ◽

Acute Infection ◽

Chronic Phase ◽

Tissue Cyst ◽

Specific Response ◽

Igg Antibodies ◽

Igg Antibody ◽

Wide Range ◽

Toxoplasmic Infection ◽

Human Infections

The recognition profile of the tissue cysts antigens by IgG antibodies was studied during acute and chronic human toxoplasmic infection. Thus the IgG response against Toxoplasma gondii was investigated by immunoblotting in two patients accidentally infected with the RH strain as well as in group of naturally infected patients at acute and chronic phase. There was an overall coincidence of molecular mass among antigens of tachyzoites and tissue cysts recognized by these sera, however, they appear not to be the same molecules. The response against tissue cysts starts early during acute infection, and the reactivity of antibodies is strong against a wide range of antigens. Six bands (between 82 and 151 kDa) were exclusively recognized by chronic phase sera but only the 132 kDa band was positive in more than 50% of the sera analysed. A mixture of these antigens could be used to discriminate between the two infection phases. The most important antigens recognized by the acute and the chronic phase sera were 4 clusters in the ranges 20-24 kDa, 34-39 kDa, 58-80 kDa and 105-130 kDa as well as two additional antigens of 18 and 29 kDa. Both accidentally infected patients and some of the naturally infected patients showed a weak specific response against tissue cyst antigens.

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Tissue cyst tropism in Toxoplasma gondii: a comparison of tissue cyst formation in organs of cats, and rodents fed oocysts

Parasitology ◽

10.1017/s0031182097008949 ◽

1997 ◽

Vol 115 (1) ◽

pp. 15-20 ◽

Cited By ~ 52

Author(s):

J. P. DUBEY

Keyword(s):

Toxoplasma Gondii ◽

Cyst Formation ◽

Tissue Cyst ◽

Intermediate Hosts ◽

Mesenteric Lymph Nodes ◽

Marked Contrast ◽

Mesenteric Lymph ◽

Time Period ◽

Rats And Mice ◽

The Brain

The persistence of Toxoplasma gondii tissue cysts in organs of cats (definitive host) and rodents (intermediate hosts) was studied. Nine cats, 12 rats, and 12 mice were fed T. gondii oocysts and their organs were digested in pepsin and then bioassayed for bradyzoites in mice. Of 9 cats killed 37 or 51 days after feeding 102 (2 cats), 103 (3 cats) or 104 (4 cats) oocysts of the VEG strain, tissue cysts were found in each cat; in the tongue of 9, in the heart of 5, in the brain of 4, and in the eyes of 1 cat. The dose had no effect on the distribution of tissue cysts in cats. Twelve rats were each fed 105 oocysts of the VEG strain of T. gondii and killed 21, 29, 64 or 237 days later. At each time-period, 11 tissues of 3 rats were pooled and bioassayed in mice. Tissue cysts were found in the brain, skeletal muscle, heart and kidneys of rats at each killing time; in the lungs, intestines, and mesenteric lymph nodes in 3 of 4 instances; in the tongue, liver, and eyes in 2 instances and in the spleen in 1 instance. Also, using the same procedures and sampling the same 11 tissues as used for rats, tissue cysts were seen in all organs except in the tongue and liver of 3 mice killed on day 82 after feeding the VEG strain. In 9 mice (3 with each strain) fed oocysts of the ME-49, GT-1, or P89 T. gondii strain and killed 62–130 days later, tissue cysts were found consistently only in the brain. Thus, in rats and mice, most tissue cysts were found in the brain and rarely in the tongue. This was in marked contrast to the distribution of tissue cysts in cats.

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Developmentally regulated biosynthesis of carbohydrate and storage polysaccharide during differentiation and tissue cyst formation in Toxoplasma gondii

Biochimie ◽

10.1016/s0300-9084(03)00076-2 ◽

2003 ◽

Vol 85 (3-4) ◽

pp. 353-361 ◽

Cited By ~ 47

Author(s):

Alexandra Coppin ◽

Florence Dzierszinski ◽

Sandra Legrand ◽

Marlène Mortuaire ◽

David Ferguson ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Cyst Formation ◽

Tissue Cyst ◽

Developmentally Regulated ◽

And Storage ◽

Storage Polysaccharide

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Toxoplasma gondii AP2IX-4 Regulates Gene Expression during Bradyzoite Development

mSphere ◽

10.1128/msphere.00054-17 ◽

2017 ◽

Vol 2 (2) ◽

Cited By ~ 22

Author(s):

Sherri Huang ◽

Michael J. Holmes ◽

Joshua B. Radke ◽

Dong-Pyo Hong ◽

Ting-Kai Liu ◽

...

Keyword(s):

Gene Expression ◽

Toxoplasma Gondii ◽

Cyst Formation ◽

Tissue Cyst ◽

Stress Induction ◽

Content Type ◽

A Cell ◽

Transitional Forms ◽

Mouse Model Of Infection ◽

Cyst Development

ABSTRACT Toxoplasma gondii is a single-celled parasite that persists in its host as a transmissible tissue cyst. How the parasite converts from its replicative form to the bradyzoites housed in tissue cysts is not well understood, but the process clearly involves changes in gene expression. Here we report that parasites lacking a cell cycle-regulated transcription factor called AP2IX-4 display reduced frequencies of tissue cyst formation in culture and in a mouse model of infection. Parasites missing AP2IX-4 lose the ability to regulate bradyzoite genes during tissue cyst development. Expressed in developing bradyzoites still undergoing division, AP2IX-4 may serve as a useful marker in the study of transitional forms of the parasite. Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. Knockout of AP2IX-4 had no discernible effect on tachyzoite replication but resulted in a reduced frequency of tissue cyst formation following alkaline stress induction—a defect that is reversible by complementation. AP2IX-4 has a complex role in regulating bradyzoite gene expression, as the levels of many bradyzoite mRNAs dramatically increased beyond those seen under conditions of normal stress induction in AP2IX-4 knockout parasites exposed to alkaline media. The loss of AP2IX-4 also resulted in a modest virulence defect and reduced cyst burden in chronically infected mice, which was reversed by complementation. These findings illustrate that the transcriptional mechanisms responsible for tissue cyst development operate across the intermediate life cycle from the dividing tachyzoite to the dormant bradyzoite. IMPORTANCE Toxoplasma gondii is a single-celled parasite that persists in its host as a transmissible tissue cyst. How the parasite converts from its replicative form to the bradyzoites housed in tissue cysts is not well understood, but the process clearly involves changes in gene expression. Here we report that parasites lacking a cell cycle-regulated transcription factor called AP2IX-4 display reduced frequencies of tissue cyst formation in culture and in a mouse model of infection. Parasites missing AP2IX-4 lose the ability to regulate bradyzoite genes during tissue cyst development. Expressed in developing bradyzoites still undergoing division, AP2IX-4 may serve as a useful marker in the study of transitional forms of the parasite.

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