scholarly journals Role of Toxoplasma gondii Myosin A in Powering Parasite Gliding and Host Cell Invasion

Science ◽  
2002 ◽  
Vol 298 (5594) ◽  
pp. 837-840 ◽  
Author(s):  
M. Meissner
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion

scholarly journals Two phosphoglucomutase paralogs regulate triggered secretion of the Toxoplasma micronemes

2017 ◽  
Author(s):  
Sudeshna Saha ◽  
Bradley I. Coleman ◽  
Tiffany Sansom ◽  
Rashmi Dubey ◽  
Ira J. Blader ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Lytic Cycle ◽  
Host Cell Invasion ◽  
Plain Language ◽  
Functional Interaction ◽  
Similar Phenotype

AbstractParafusin is a phosphoglucomutase (PGM) paralog that acts as a signaling scaffold protein in calcium mediated exocytosis across many eukaryotes. In Toxoplasma gondii the parafusin related protein 1 (PRP1) has been associated in indirect and heterologous studies with the regulated exocytosis of the micronemes, which are required for successful host cell invasion and egress. Here we directly assessed the role of PRP1 by deleting the gene from the parasite. We observed a specific defect in microneme secretion in response to high Ca2+ fluxes, but not to phosphatidic acid fluxes controlling microneme release. We observed no defect in constitutive microneme secretion which was sufficient to support completion of the lytic cycle. Furthermore, deletion of the other PGM in Toxoplasma, PGM2, as well as the double PRP1/PGM2 deletion resulted in a similar phenotype. This suggests a functional interaction between these two genes. Strikingly, tachyzoites without both paralogs are completely viable in vitro and during acute mice infections. This indicates that PGM activity is neither required for glycolysis. In conclusion, the PRP1-PGM2 pair is required for a burst in microneme secretion upon high Ca2+ fluxes, but this burst is not essential to complete the lytic cycle of the parasite.Plain Language SummaryCalcium mediated control of microneme secretion is essential for host cell invasion and egress of Toxoplasma gondii. Here it is shown that the two phosphoglucomutases in Toxoplasma both function in the translation of a spike in calcium into a burst in microneme secretion.

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 and intracellular residence by Aeromonas salmonicida: Role of the S-layer

2000 ◽  
Vol 46 (7) ◽  
pp. 660-668 ◽  
Author(s):  
Rafael A. Garduño ◽  
Anne R. Moore ◽  
Gilles Olivier ◽  
Angela L. Lizama ◽  
Elizabeth Garduño ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Invasion ◽  
Aeromonas Salmonicida ◽  
Host Cell Invasion
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