|
| Status |
Public on May 22, 2024 |
| Title |
A potent HDAC inhibitor blocks Toxoplasma gondii tachyzoite growth and profoundly disrupts parasite gene expression. |
| Organism |
Toxoplasma gondii |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Toxoplasmosis is a major health issue worldwide especially for immune-deficient individuals and the offspring of newly infected mothers. It is caused by a unicellular intracellular parasite called Toxoplasma gondii. Although the drugs commonly used to treat toxoplasmosis are efficient, they present serious side effects and adverse events are common. Therefore, there is a need for the discovery of new compounds with potent anti-T. gondii activity. We have tested compounds designed to target enzymes that are involved in the epigenetic regulation of gene expression. Among the most active compounds, we identified a HDAC inhibitor that shows an IC50 of around 30 nM with a selectivity index of more than 100. MC1742 is active at inhibiting the growth of the parasite in vitro but also at preventing the consequences of the acute disease in vivo. This compound induces a hyper-acetylation of histones while acetylated tubulin level remains unchanged. After MC1742 treatment, the parasite expression profile is profoundly changed with the activation of genes preferentially expressed in the sexual stages that are normally repressed at the tachyzoite stage. These findings suggest that this compound disturbs the T. gondii gene expression program, inducing parasite death.
|
| |
|
| Overall design |
Three biological replicate of theparasite T. gondii tachyzoites treated with DMSO or MC1742. mRNA profiles were generated by high throughput sequencing using HiSeq 2500 system (Illumina).
|
| |
|
| Contributor(s) |
GISSOT M, Mouveaux T |
| Citation(s) |
35041939 |
| |
| Submission date |
Jun 01, 2021 |
| Last update date |
May 22, 2024 |
| Contact name |
Mathieu Gissot |
| Organization name |
CNRS
|
| Department |
CIIL- UMR 8204 - U1019
|
| Lab |
Biology of Apicomplexan Parasites
|
| Street address |
1, rue du Pr. calmette
|
| City |
Lille |
| ZIP/Postal code |
59000 |
| Country |
France |
| |
|
| Platforms (1) |
| GPL23377 |
Illumina HiSeq 2500 (Toxoplasma gondii) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA734301 |
| SRA |
SRP322156 |
Less...
More...