ArticleAntimicrobial agents and chemotherapy2016
Garcinol Inhibits GCN5-Mediated Lysine Acetyltransferase Activity and Prevents Replication of the Parasite Toxoplasma gondii.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Toxoplasma gondii SIR2A Promotes Tachyzoite Invasion via Lysine Deacetylase Activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Parasite-specific essential bromodomain protein TgBDP4 is a key epigenetic reader and a potential drug target for the parasite Toxoplasma gondii.The Journal of biological chemistry · 2026Article
- Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire.Proteomics · 2025Review
- Article
- The essential kinase TgGSK regulates centrosome division and endodyogeny inbioRxiv : the preprint server for biology · 2024Article
- Analysis of the role of acetylation inFrontiers in microbiology · 2024Article
- Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Article
- Histone variant H2B.Z acetylation is necessary for maintenance ofbioRxiv : the preprint server for biology · 2023Article
- Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases.Frontiers in oncology · 2022Review
- Protein acetylation in the critical biological processes in protozoan parasites.Trends in parasitology · 2021Review
- Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.Angewandte Chemie (International ed. in English) · 2021Article
- Histone acetyltransferase PfGCN5 regulates stress responsive and artemisinin resistance related genes in Plasmodium falciparum.Scientific reports · 2021Article
- Phytochemicals and Biological Activities ofMolecules (Basel, Switzerland) · 2020Review
- Evaluating the GCN5b bromodomain as a novel therapeutic target against the parasite Toxoplasma gondii.Experimental parasitology · 2020Article
- Exploring the Histone Acetylation Cycle in the Protozoan ModelFrontiers in cell and developmental biology · 2020Review
- Safety profile of 40% Garcinol fromToxicology reports · 2018Article
- Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development.Microbiology and molecular biology reviews : MMBR · 2017Review
- Drugs in development for toxoplasmosis: advances, challenges, and current status.Drug design, development and therapy · 2017Review
- Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity.Antimicrobial agents and chemotherapy · 2016Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Lysine acetylation is a critical posttranslational modification that influences protein activity, stability, and binding properties. The acetylation of histone proteins in particular is a well-characterized feature of gene expression regulation. In the protozoan parasiteToxoplasma gondii, a number of lysine acetyltransferases (KATs) contribute to gene expression and are essential for parasite viability. The natural product garcinol was recently reported to inhibit enzymatic activities of GCN5 and p300 family KATs in other species. Here we show that garcinol inhibits TgGCN5b, the only nuclear GCN5 family KAT known to be required forToxoplasmatachyzoite replication. Treatment of tachyzoites with garcinol led to a reduction of global lysine acetylation, particularly on histone H3 and TgGCN5b itself. We also performed transcriptome sequencing (RNA-seq), which revealed increasing aberrant gene expression coincident with increasing concentrations of garcinol. The majority of the genes that were most significantly affected by garcinol were also associated with TgGCN5b in a previously reported chromatin immunoprecipitation assay with microarray technology (ChIP-chip) analysis. The dysregulated gene expression induced by garcinol significantly inhibitsToxoplasmatachyzoite replication, and the concentrations used exhibit no overt toxicity on human host cells. Garcinol also inhibitsPlasmodium falciparumasexual replication with a 50% inhibitory concentration (IC50) similar to that forToxoplasma Together, these data support that pharmacological inhibition of TgGCN5b leads to a catastrophic failure in gene expression control that prevents parasite replication.
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