scholarly journals Ionophore-stimulation promotes re-organization of the invasion machinery of Toxoplasma gondii

2022 ◽  
Author(s):  
Li-av Segev-Zarko ◽  
Peter D. Dahlberg ◽  
Stella Y. Sun ◽  
Daniël M. Pelt ◽  
James A. Sethian ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cell Invasion ◽  
Electron Tomography ◽  
Calcium Ionophore ◽  
Host Cell Invasion ◽  
Fusion Event ◽  
Important Species ◽  
Subcellular Organelles ◽  
Present Information ◽  
The Many

Host cell invasion by intracellular, eukaryotic parasites, like the many important species within the phylum Apicomplexa, is a remarkable and active process involving the coordinated action of many apical organelles and other structures. To date, capturing how these various structures interact during invasion has been difficult to observe in detail. Here, we used cryogenic electron tomography to generate images of the apical complex of Toxoplasma gondii tachyzoites under conditions that mimic resting parasites and those primed to invade through addition of a calcium ionophore. Using AI-based image-processing we were able to annotate 48 tomograms to identify and extract densities of the relevant subcellular organelles and accurately analyze features in 3D. We describe an interaction between an anteriorly located apical vesicle and a rhoptry tip that occurs only in the ionophore-stimulated parasites and that is associated with dramatic changes in the vesicle's shape in what appears to be a stalled fusion event. We also present information to support the presumption that this vesicle originates from the well-described vesicles that parallel the intraconoidal microtubules and that the latter two structures are linked by a novel tether. Lastly, we show that a previously described rosette is found associated with more than just the anterior-most apical vesicle, indicating that multiple such vesicles are primed to enable rhoptry secretion.

Calcium ionophore-induced egress of Toxoplasma gondii shortly after host cell invasion

2007 ◽  
Vol 147 (3-4) ◽  
pp. 210-220 ◽  
Author(s):  
Lucio Ayres Caldas ◽  
Wanderley de Souza ◽  
Márcia Attias
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Calcium Ionophore ◽  
Host Cell Invasion

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.

Host cell invasion by Toxoplasma gondii

1998 ◽  
Vol 6 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Jean François Dubremetz
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion

MIC6 associates with aldolase in host cell invasion by Toxoplasma gondii

2009 ◽  
Vol 105 (2) ◽  
pp. 441-445 ◽  
Author(s):  
Bin Zheng ◽  
Ai He ◽  
Ming Gan ◽  
Zhouya Li ◽  
Hualiang He ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion

scholarly journals Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii

2010 ◽  
Vol 6 (10) ◽  
pp. e1001132 ◽  
Author(s):  
Wassim Daher ◽  
Fabienne Plattner ◽  
Marie-France Carlier ◽  
Dominique Soldati-Favre
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Gliding Motility ◽  
Host Cell Invasion ◽  
Concerted Action

scholarly journals Not a Simple Tether: Binding of Toxoplasma gondii AMA1 to RON2 during Invasion Protects AMA1 from Rhomboid-Mediated Cleavage and Leads to Dephosphorylation of Its Cytosolic Tail

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Shruthi Krishnamurthy ◽  
Bin Deng ◽  
Roxana del Rio ◽  
Kerry R. Buchholz ◽  
Moritz Treeck ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Transmembrane Domain ◽  
Critical Role ◽  
Host Cells ◽  
Receptor Protein ◽  
Host Cell Invasion ◽  
Cell Binding ◽  
Apicomplexan Parasites

ABSTRACT Apical membrane antigen 1 (AMA1) is a receptor protein on the surface of Toxoplasma gondii that plays a critical role in host cell invasion. The ligand to which T . gondii AMA1 (TgAMA1) binds, TgRON2, is secreted into the host cell membrane by the parasite during the early stages of invasion. The TgAMA1-TgRON2 complex forms the core of the “moving junction,” a ring-shaped zone of tight contact between the parasite and host cell membranes, through which the parasite pushes itself during invasion. Paradoxically, the parasite also expresses rhomboid proteases that constitutively cleave the TgAMA1 transmembrane domain. How can TgAMA1 function effectively in host cell binding if its extracellular domain is constantly shed from the parasite surface? We show here that when TgAMA1 binds the domain 3 (D3) peptide of TgRON2, its susceptibility to cleavage by rhomboid protease(s) is greatly reduced. This likely serves to maintain parasite-host cell binding at the moving junction, a hypothesis supported by data showing that parasites expressing a hypercleavable version of TgAMA1 invade less efficiently than wild-type parasites do. Treatment of parasites with the D3 peptide was also found to reduce phosphorylation of S527 on the cytoplasmic tail of TgAMA1, and parasites expressing a phosphomimetic S527D allele of TgAMA1 showed an invasion defect. Taken together, these data suggest that TgAMA1-TgRON2 interaction at the moving junction protects TgAMA1 molecules that are actively engaged in host cell penetration from rhomboid-mediated cleavage and generates an outside-in signal that leads to dephosphorylation of the TgAMA1 cytosolic tail. Both of these effects are required for maximally efficient host cell invasion. IMPORTANCE Nearly one-third of the world’s population is infected with the protozoan parasite Toxoplasma gondii , which causes life-threatening disease in neonates and immunocompromised individuals. T. gondii is a member of the phylum Apicomplexa, which includes many other parasites of veterinary and medical importance, such as those that cause coccidiosis, babesiosis, and malaria. Apicomplexan parasites grow within their hosts through repeated cycles of host cell invasion, parasite replication, and host cell lysis. Parasites that cannot invade host cells cannot survive or cause disease. AMA1 is a highly conserved protein on the surface of apicomplexan parasites that is known to be important for invasion, and the work presented here reveals new and unexpected insights into AMA1 function. A more complete understanding of the role of AMA1 in invasion may ultimately contribute to the development of new chemotherapeutics designed to disrupt AMA1 function and invasion-related signaling in this important group of human pathogens.

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