Toxoplasma gondii Parasites Take Control within Host Cells

2012 ◽  
Vol 7 (8) ◽  
pp. 360-365
Author(s):  
Eric Y. Denkers ◽  
Barbara A. Butcher
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cells

Toxoplasma Gondii Bradyzoites Elicit Transcriptional Changes in Host Cells to Prevent IFNγ-Mediated Cell Death

2019 ◽  
Author(s):  
Simona Seizova ◽  
Alexandra L Garnham ◽  
Michael J Coffey ◽  
Lachlan W Whitehead ◽  
Kelly L Rogers ◽  
...  
Keyword(s):  
Cell Death ◽  
Toxoplasma Gondii ◽  
Host Cells ◽  
Transcriptional Changes

scholarly journals Loss of a conserved MAPK causes catastrophic failure in assembly of a specialized cilium-like structure in Toxoplasma gondii

2020 ◽  
Vol 31 (9) ◽  
pp. 881-888 ◽  
Author(s):  
William J. O’Shaughnessy ◽  
Xiaoyu Hu ◽  
Tsebaot Beraki ◽  
Matthew McDougal ◽  
Michael L. Reese
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cells ◽  
Ultrastructural Changes ◽  
Catastrophic Failure ◽  
Replicative Cycle

Toxoplasma gondii that lacks the kinase ERK7 cannot invade or egress from their host cells, thereby blocking their replicative cycle. These defects are due to the loss of a specialized cilium-like structure called the conoid. Strikingly, the ultrastructural changes are specific to the conoid, and suggest an important role for ERK7 in its biogenesis.

scholarly journals Toxoplasma gondii actively remodels the microtubule network in host cells

2008 ◽  
Vol 10 (14-15) ◽  
pp. 1440-1449 ◽  
Author(s):  
Margaret E. Walker ◽  
Elizabeth E. Hjort ◽  
Sherri S. Smith ◽  
Abhishek Tripathi ◽  
Jessica E. Hornick ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cells ◽  
Microtubule Network

scholarly journals 1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1053
Author(s):  
Lidia Węglińska ◽  
Adrian Bekier ◽  
Katarzyna Dzitko ◽  
Barbara Pacholczyk-Sienicka ◽  
Łukasz Albrecht ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Direct Action ◽  
Human Fibroblasts ◽  
Imidazole Ring ◽  
Host Cells ◽  
In Vitro Assays ◽  
Host Cell Invasion

Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b–12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b–12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells.

Microtubules, but not actin filaments, drive daughter cell budding and cell division in Toxoplasma gondii

2000 ◽  
Vol 113 (7) ◽  
pp. 1241-1254 ◽  
Author(s):  
M.K. Shaw ◽  
H.L. Compton ◽  
D.S. Roos ◽  
L.G. Tilney
Keyword(s):  
Toxoplasma Gondii ◽  
Actin Cytoskeleton ◽  
Daughter Cell ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Actin Dynamics ◽  
Residual Body ◽  
Cell Organelles ◽  
Infection Period ◽  
Parasite Replication

We have used drugs to examine the role(s) of the actin and microtubule cytoskeletons in the intracellular growth and replication of the intracellular protozoan parasite, Toxoplasma gondii. By using a 5 minute infection period and adding the drugs shortly after entry we can treat parasites at the start of intracellular development and 6–8 hours prior to the onset of daughter cell budding. Using this approach we found, somewhat surprisingly, that reagents that perturb the actin cytoskeleton in different ways (cytochalasin D, latrunculin A and jasplakinolide) had little effect on parasite replication although they had the expected effects on the host cells. These actin inhibitors did, however, disrupt the orderly turnover of the mother cell organelles leading to the formation of a large residual body at the posterior end of each pair of budding parasites. Treating established parasite cultures with the actin inhibitors blocked ionophore-induced egression of tachyzoites from the host cells, demonstrating that intracellular parasites were susceptible to the effects of these inhibitors. In contrast, the anti-microtubule drugs oryzalin and taxol, and to a much lesser extent nocodazole, which affect microtubule dynamics in different ways, blocked parasite replication by disrupting the normal assembly of the apical conoid and the microtubule inner membrane complex (IMC) in the budding daughter parasites. Centrosome replication and assembly of intranuclear spindles, however, occurred normally. Thus, daughter cell budding per se is dependent primarily on the parasite microtubule system and does not require a dynamic actin cytoskeleton, although disruption of actin dynamics causes problems in the turnover of parasite organelles.

scholarly journals Reduction in the mitochondrial membrane potential of Toxoplasma gondii after invasion of host cells

1984 ◽  
Vol 70 (1) ◽  
pp. 73-81
Author(s):  
K. Tanabe ◽  
K. Murakami
Keyword(s):  
Membrane Potential ◽  
Toxoplasma Gondii ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Protozoan Parasite ◽  
Fluorescent Dye ◽  
Host Cells ◽  
Intracellular Parasites ◽  
Neutral Compounds ◽  
Infected Cells

The membrane potential of Toxoplasma gondii, an obligatory intracellular protozoan parasite, was monitored with the cationic permeant fluorescent dye rhodamine 123 (R123). Fluorescence microscopy revealed R123 to be partitioned predominantly in a restricted part of the parasite, which consisted of twisted or branched tubules, or of granular bodies. These structures were frequently connected to each other. The dye retention by these structures was markedly reduced by treating R123-labelled parasites with the proton ionophore, carbonylcyanide m-chlorophenylhydrazone, the potassium ionophore, valinomycin and the inhibitor of electron transport, antimycin A. Thus, these structures are regarded as the parasite mitochondria. Another cationic fluorescent dye, rhodamine 6G, stained the parasite mitochondria, whereas a negatively charged fluorescent dye, fluorescein, and the neutral compounds, rhodamine 110 and rhodamine B, did not. This fact indicates that R123 monitored the parasite mitochondrial membrane potential. T. gondii-infected 3T3 cells were also stained with R123. In contrast to the mitochondria of extracellular parasites, those of intracellular parasites failed to take up the dye. The absence of fluorescence in intracellular parasites persisted until the infected host cells ruptured and liberated daughter parasites 1 day after infection. Parasites, liberated from the host cells, either spontaneously or artificially by passing the infected cells through a 27G needle, regained the ability to take up the dye. After direct microinjection of R123 into the vacuole in which the parasite grows and multiples, the dye appeared in the host-cell mitochondria but not in the parasite's mitochondria. Thus, we conclude that the mitochondrial membrane potential of T. gondii was reduced after invasion of host cells by the parasite.

TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2

2001 ◽  
Vol 41 (3) ◽  
pp. 537-547 ◽  
Author(s):  
Karen E. Rabenau ◽  
Afshin Sohrabi ◽  
Ashutosh Tripathy ◽  
Christopher Reitter ◽  
James W. Ajioka ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cells ◽  
Adhesive Protein

scholarly journals Toxoplasma gondii Rhoptry Discharge Correlates with Activation of the Early Growth Response 2 Host Cell Transcription Factor

2008 ◽  
Vol 76 (10) ◽  
pp. 4703-4712 ◽  
Author(s):  
Eric D. Phelps ◽  
Kristin R. Sweeney ◽  
Ira J. Blader
Keyword(s):  
Transcription Factor ◽  
Toxoplasma Gondii ◽  
Host Cell ◽  
Growth Response ◽  
Neospora Caninum ◽  
Early Growth ◽  
Apicomplexan Parasite ◽  
Host Cells ◽  
Early Growth Response ◽  
Cell Extracts

ABSTRACT Toxoplasma gondii is a ubiquitous apicomplexan parasite that can cause severe disease in fetuses and immune-compromised patients. Rhoptries, micronemes, and dense granules, which are secretory organelles unique to Toxoplasma and other apicomplexan parasites, play critical roles in parasite growth and virulence. To understand how these organelles modulate infected host cells, we sought to identify host cell transcription factors triggered by their release. Early growth response 2 (EGR2) is a host cell transcription factor that is rapidly upregulated and activated in Toxoplasma-infected cells but not in cells infected with the closely related apicomplexan parasite Neospora caninum. EGR2 upregulation occurred only when live parasites were in direct contact with the host cell and not from exposure to cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pretreating parasites with a calcium chelator, EGR2 expression was significantly reduced. In contrast, when host cells were infected with parasites in the presence of cytochalasin D, which allows rhoptry secretion but prevents parasite invasion, EGR2 was activated. Finally, we demonstrate that Toxoplasma activation of host p38 mitogen-activated protein kinase is necessary but not sufficient for EGR2 activation. Collectively, these data indicate that EGR2 is specifically upregulated by a parasite-derived secreted factor that is most likely a resident rhoptry protein.

scholarly journals A Toxoplasma gondii Class XIV Myosin, Expressed in Sf9 Cells with a Parasite Co-chaperone, Requires Two Light Chains for Fast Motility

2014 ◽  
Vol 289 (44) ◽  
pp. 30832-30841 ◽  
Author(s):  
Carol S. Bookwalter ◽  
Anne Kelsen ◽  
Jacqueline M. Leung ◽  
Gary E. Ward ◽  
Kathleen M. Trybus
Keyword(s):  
Toxoplasma Gondii ◽  
Light Chain ◽  
Function Analysis ◽  
Expression System ◽  
Host Cells ◽  
Light Chains ◽  
Essential Light Chain ◽  
Heterologous System ◽  
Tetratricopeptide Repeat Domain ◽  
Cell Expression

Many diverse myosin classes can be expressed using the baculovirus/Sf9 insect cell expression system, whereas others have been recalcitrant. We hypothesized that most myosins utilize Sf9 cell chaperones, but others require an organism-specific co-chaperone. TgMyoA, a class XIVa myosin from the parasite Toxoplasma gondii, is required for the parasite to efficiently move and invade host cells. The T. gondii genome contains one UCS family myosin co-chaperone (TgUNC). TgMyoA expressed in Sf9 cells was soluble and functional only if the heavy and light chain(s) were co-expressed with TgUNC. The tetratricopeptide repeat domain of TgUNC was not essential to obtain functional myosin, implying that there are other mechanisms to recruit Hsp90. Purified TgMyoA heavy chain complexed with its regulatory light chain (TgMLC1) moved actin in a motility assay at a speed of ∼1.5 μm/s. When a putative essential light chain (TgELC1) was also bound, TgMyoA moved actin at more than twice that speed (∼3.4 μm/s). This result implies that two light chains bind to and stabilize the lever arm, the domain that amplifies small motions at the active site into the larger motions that propel actin at fast speeds. Our results show that the TgMyoA domain structure is more similar to other myosins than previously appreciated and provide a molecular explanation for how it moves actin at fast speeds. The ability to express milligram quantities of a class XIV myosin in a heterologous system paves the way for detailed structure-function analysis of TgMyoA and identification of small molecule inhibitors.

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