scholarly journals Epichromatin is conserved in Toxoplasma gondii and labels the exterior parasite chromatin throughout the cell cycle

Parasitology ◽  
2013 ◽  
Vol 140 (9) ◽  
pp. 1104-1110 ◽  
Author(s):  
LAURA VANAGAS ◽  
MARIA C. DALMASSO ◽  
JEAN F. DUBREMETZ ◽  
ENRIQUE L. PORTIANSKY ◽  
DONALD E. OLINS ◽  
...  

SUMMARYToxoplasma gondii is an apicomplexan intracellular protozoan parasite responsible for toxoplasmosis, a disease with considerable medical and economic impact worldwide. Toxoplasma gondii cells never lose the nuclear envelope and their chromosomes do not condense. Here, we tested the murine monoclonal antibody PL2-6, which labels epichromatin (a conformational chromatin epitope based on histones H2A and H2B complexed with DNA), in T. gondii cultured in human fibroblasts. This epitope is present at the exterior chromatin surface of interphase nuclei and on the periphery of mitotic chromosomes in higher eukaryotes. PL2-6 reacted with T. gondii H2A and H2B histones in Western blot (WB) assays. In addition, the antibody reacted with the nuclear fraction of tachyzoites, as a single band coincident with H2B histone. In the T. gondii tachyzoite stage, PL2-6 also had peripheral nuclear localization, as observed by epifluorescence/confocal microscopy and immunoelectron microscopy. Confocal analysis showed that epichromatin is slightly polarized to one face of the parasite exterior chromatin surface. In replicating tachyzoites, PL2-6 also labels the exterior chromatin surface, covering the face of both segregating nuclei, facing the plasma membrane of the mother cell. The possible role of epichromatin in T. gondii is discussed.

2019 ◽  
Vol 3 (1) ◽  
pp. e201900549 ◽  
Author(s):  
Youngae Lee ◽  
Hiroshi Yamada ◽  
Ariel Pradipta ◽  
Ji Su Ma ◽  
Masaaki Okamoto ◽  
...  

Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting warm-blooded animals by ingestion. The organism enters host cells and resides in the cytoplasm in a membrane-bound parasitophorous vacuole (PV). Inducing an interferon response enables IFN-γ–inducible immunity-related GTPase (IRG protein) to accumulate on the PV and to restrict parasite growth. However, little is known about the mechanisms by which IRG proteins recognize and destroy T. gondii PV. We characterized the role of IRG protein Irgb6 in the cell-autonomous response against T. gondii, which involves vacuole ubiquitination and breakdown. We show that Irgb6 is capable of binding a specific phospholipid on the PV membrane. Furthermore, the absence of Irgb6 causes reduced targeting of other effector IRG proteins to the PV. This suggests that Irgb6 has a role as a pioneer in the process by which multiple IRG proteins access the PV. Irgb6-deficient mice are highly susceptible to infection by a strain of T. gondii avirulent in wild-type mice.


Parasitology ◽  
2011 ◽  
Vol 138 (6) ◽  
pp. 691-697 ◽  
Author(s):  
M. RASSOULI ◽  
G. R. RAZMI ◽  
M. R. BASSAMI ◽  
A. R. MOVASSAGHI ◽  
M. AZIZZADEH

SUMMARYToxoplasma gondii, an obligatory intracellular protozoan parasite, is one of the causative agents of ovine abortion, as reported in many countries. Different techniques are being used to detect this pathogen in infected ovine fetuses. One of the most sensitive and specific diagnostic techniques is Nested-PCR amplification of the B1 target gene of the organism. In total, 200 brain samples of aborted ovine fetuses and maternal sera submitted from different parts of Khorasan Razavi province, Iran were investigated to track the role ofToxoplasma gondiiin ovine abortion by a slightly modified Nested-PCR and IFAT assays, respectively. Among all samples, 27 (13·5%) were PCR-positive and 31 (15·5%) were IFAT-positive and theToxoplasma-induced abortion prevalence calculated was 8·8% to18·2% with 95% confidence interval. Results show that high levels of congenital transmission may occur in 27/31(87%) of pregnancies with an excellent logical agreement (ĸ=0·9) between 2 different tests. According to the results of this study, the Nested-PCR employed in this investigation could be recommended as an applied routine test for the routine examination and confirmation ofToxoplasma gondii-induced ovine abortion.


Parasitology ◽  
2017 ◽  
Vol 145 (2) ◽  
pp. 148-155 ◽  
Author(s):  
A. Q. I. ALQAISI ◽  
A. J. MBEKEANI ◽  
M. BASSAS LLORENS ◽  
A. P. ELHAMMER ◽  
P. W. DENNY

SUMMARYToxoplasma gondii is an obligate intracellular protozoan parasite of the phylum Apicomplexa, and toxoplasmosis is an important disease of both humans and economically important animals. With a limited array of drugs available there is a need to identify new therapeutic compounds. Aureobasidin A (AbA) is an antifungal that targets the essential inositol phosphorylceramide (IPC, sphingolipid) synthase in pathogenic fungi. This natural cyclic depsipeptide also inhibits Toxoplasma proliforation, with the protozoan IPC synthase orthologue proposed as the target. The data presented here show that neither AbA nor an analogue (Compound 20), target the protozoan IPC synthase orthologue or total parasite sphingolipid synthesis. However, further analyses confirm that AbA exhibits significant activity against the proliferative tachyzoite form of Toxoplasma, and Compound 20, whilst effective, has reduced efficacy. This difference was more evident on analyses of the direct effect of these compounds against isolated Toxoplasma, indicating that AbA is rapidly microbicidal. Importantly, the possibility of targeting the encysted, bradyzoite, form of the parasite with AbA and Compound 20 was demonstrated, indicating that this class of compounds may provide the basis for the first effective treatment for chronic toxoplasmosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Mitra Salehi ◽  
Hosein Nezami ◽  
Hamid Reza Niazkar

Toxoplasma gondii is a zoonotic obligate intracellular protozoan parasite that infects warm-blooded animals as well as humans worldwide. The purpose of this study was to delineate the prevalence of Toxoplasma infection in aborted fetuses of sheep in North Khorasan province, Iran. Three hundred and ninety-nine samples of the liver (133 samples), placenta (133 samples), and brain (133 samples) from 133 aborted fetuses of sheep were collected from 2015 to 2017. The ages of aborted fetuses were higher than 120 days’ gestational age in this study. According to the samples, sixteen out of 133 aborted fetuses of sheep were infected with T. gondii. Toxoplasma DNA was found in the placenta (68.75%) and liver (31.25%) samples of infected fetuses using the PCR method. The highest and lowest rates of Toxoplasma infection were observed during 2016 and 2017, respectively. Shirvan and Faruj provinces were recognized as the two most infected districts among others. There was a significant difference between the year and abortion rate in sheep due to infection by the Toxoplasma parasite (P<0.05). Furthermore, no significant difference between the prevalence of T. gondii infection and aborted fetuses was seen (P>0.05) in different areas. According to the present study, T. gondii infection can be one of the causes of fetus abortion of sheep in North Khorasan province, Iran.


2018 ◽  
Vol 1 (3) ◽  
pp. 5-11
Author(s):  
Abdulghani M. Alsamarai ◽  
Hala M. Hassan

Toxoplasmosis is caused by infection with the obligated intracellular protozoan parasite Toxoplasma gondii. It is one of the most prevalent chronic infections affecting one third of the world's human population. The prevalence of T. gondii infection varies among different geographical regions. The infection is characterized by non-specific signs with the consequent formation of cysts that may stay in latent form in many organs. Primary infection is usually subclinical but in some patient's cervical lymphoadenopathy or ocular disease can be present. Rubella is a mild disease caused by a togavirus. There may be a mild prodromal illness involving a low-grade fever, malaise, coryza and mild conjunctivitis. Lymphadenopathy involving post-auricular and sub-occipital glands may lead to rash. The rash is usually transitory, erythematous and mostly seen behind the ears and on the face and neck. Clinical diagnosis is unreliable as the rash may be fleeting and is not specific to rubella. Rubella is spread by droplet transmission. The incubation period is 14 to 21 days, with the majority of individuals developing a rash 14 to 17 days after exposure. Individuals with rubella are infectious from one week before symptoms appear to four days after the onset of the rash. Complications include thrombocytopaenia (the rate may be as high as one in 3000 infections) and post-infectious encephalitis (one in 6000 cases).


mSphere ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Joseph M. Varberg ◽  
Leah R. Padgett ◽  
Gustavo Arrizabalaga ◽  
William J. Sullivan

ABSTRACT Toxoplasma gondii is an opportunistic parasite that infects at least one-third of the world population. New treatments for the disease (toxoplasmosis) are needed since current drugs are toxic to patients. Microtubules are essential cellular structures built from tubulin that show promise as antimicrobial drug targets. Microtubules can be regulated by chemical modification, such as acetylation on lysine 40 (K40). To determine the role of K40 acetylation in Toxoplasma and whether it is a liability to the parasite, we performed mutational analyses of the α-tubulin gene. Our results indicate that parasites cannot survive without K40 acetylation unless microtubules are stabilized with a secondary mutation. Additionally, we identified the parasite enzyme that acetylates α-tubulin (TgATAT). Genetic disruption of TgATAT caused severe defects in parasite replication, further highlighting the importance of α-tubulin K40 acetylation in Toxoplasma and its promise as a potential new drug target. Toxoplasma gondii is a widespread protozoan parasite that causes potentially life-threatening opportunistic disease. New inhibitors of parasite replication are urgently needed, as the current antifolate treatment is also toxic to patients. Microtubules are essential cytoskeletal components that have been selectively targeted in microbial pathogens; further study of tubulin in Toxoplasma may reveal novel therapeutic opportunities. It has been noted that α-tubulin acetylation at lysine 40 (K40) is enriched during daughter parasite formation, but the impact of this modification on Toxoplasma division and the enzyme mediating its delivery have not been identified. We performed mutational analyses to provide evidence that K40 acetylation stabilizes Toxoplasma microtubules and is required for parasite replication. We also show that an unusual Toxoplasma homologue of α-tubulin acetyltransferase (TgATAT) is expressed in a cell cycle-regulated manner and that its expression peaks during division. Disruption of TgATAT with CRISPR/Cas9 ablates K40 acetylation and induces replication defects; parasites appear to initiate mitosis yet exhibit incomplete or improper nuclear division. Together, these findings establish the importance of tubulin acetylation, exposing a new vulnerability in Toxoplasma that could be pharmacologically targeted. IMPORTANCE Toxoplasma gondii is an opportunistic parasite that infects at least one-third of the world population. New treatments for the disease (toxoplasmosis) are needed since current drugs are toxic to patients. Microtubules are essential cellular structures built from tubulin that show promise as antimicrobial drug targets. Microtubules can be regulated by chemical modification, such as acetylation on lysine 40 (K40). To determine the role of K40 acetylation in Toxoplasma and whether it is a liability to the parasite, we performed mutational analyses of the α-tubulin gene. Our results indicate that parasites cannot survive without K40 acetylation unless microtubules are stabilized with a secondary mutation. Additionally, we identified the parasite enzyme that acetylates α-tubulin (TgATAT). Genetic disruption of TgATAT caused severe defects in parasite replication, further highlighting the importance of α-tubulin K40 acetylation in Toxoplasma and its promise as a potential new drug target.


2020 ◽  
Vol 58 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Jina lee ◽  
Jae-Won Choi ◽  
Hye Young Han ◽  
Woo Sik Kim ◽  
Ha-Yeon Song ◽  
...  

<i>Toxoplasma gondii</i> is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with <i>T. gondii</i> and the proliferation of <i>T. gondii</i> in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of <i>T. gondii</i> parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.


Author(s):  
Osman Ergene ◽  
Bekir Celebi ◽  
Ibrahim Kucukaslan

The objective of this study was to determine the seroprevalance of canine brucellosis and toxoplasmosis in female and male dogs and also determine the realtionship to various factors as parity, abortion and pyometra. Brucella canis is a disease of the reproductive tract that may cause late abortion, infertility and fail of conception with optimum insemination time in females and infection of the sexual organs in males. Toxoplasma gondii is an important obligate intracellular protozoan parasite which can affect all warm-blooded mammals and humans which may cause fatal diseases with severe problems, such as abortion. As a result, in this study B. canis was determined in low seroprevalence in some cases on the island (North Cyprus), T. gondii was determined as an important contagious parasite. Also reproductive parameters like parity, spaying, cyclicity could be important too and it was presented that extended evaluation of these factors is needed with further studies.


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