ArticleAntimicrobial agents and chemotherapy2015
Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular characterization and protective efficacy of silent information regulator 2A from Eimeria tenella.Parasites & vectors · 2016Trial
- Article
- Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus.Communications biology · 2024Article
- Article
- Protein acetylation in the critical biological processes in protozoan parasites.Trends in parasitology · 2021Review
- The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors.Oxidative medicine and cellular longevity · 2021Review
- Mitochondrial Sirtuin TcSir2rp3 Affects TcSODA Activity and Oxidative Stress Response inFrontiers in cellular and infection microbiology · 2021Article
- Sirtuin Control of Mitochondrial Dysfunction, Oxidative Stress, and Inflammation in Chagas Disease Models.Frontiers in cellular and infection microbiology · 2021Review
- The role of the Acanthamoeba castellanii Sir2-like protein in the growth and encystation of Acanthamoeba.Parasites & vectors · 2020Article
- Identification of Inhibitors toInternational journal of molecular sciences · 2020Article
- Chemical Constituents ofMolecules (Basel, Switzerland) · 2019Article
- Histone deacetylases as targets for antitrypanosomal drugs.Future science OA · 2018Review
- Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.PLoS neglected tropical diseases · 2018Article
- The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani growth and infectivity.PLoS neglected tropical diseases · 2017Article
- Comparative effects of histone deacetylases inhibitors and resveratrol on Trypanosoma cruzi replication, differentiation, infectivity and gene expression.International journal for parasitology. Drugs and drug resistance · 2017Article
- Quantitative Proteomic Analysis of Replicative and Nonreplicative Forms Reveals Important Insights into Chromatin Biology of Trypanosoma cruzi.Molecular & cellular proteomics : MCP · 2017Article
- Chemogenetic Characterization of Inositol Phosphate Metabolic Pathway Reveals Druggable Enzymes for Targeting Kinetoplastid Parasites.Cell chemical biology · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetylation of lysine is a major posttranslational modification of proteins and is catalyzed by lysine acetyltransferases, while lysine deacetylases remove acetyl groups. Among the deacetylases, the sirtuins are NAD(+)-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting the proliferation of tumor cells, in this study, we investigated the role of these inhibitors in the growth and differentiation of Trypanosoma cruzi, the agent of Chagas disease. We found that the use of salermide during parasite infection prevented growth and initial multiplication after mammalian cell invasion by T. cruzi at concentrations that did not affect host cell viability. In addition, in vivo infection was partially controlled upon administration of salermide. There are two sirtuins in T. cruzi, TcSir2rp1 and TcSir2rp3. By using specific antibodies and cell lines overexpressing the tagged versions of these enzymes, we found that TcSir2rp1 is localized in the cytosol and TcSir2rp3 in the mitochondrion. TcSir2rp1 overexpression acts to impair parasite growth and differentiation, whereas the wild-type version of TcSir2rp3 and not an enzyme mutated in the active site improves both. The effects observed with TcSir2rp3 were fully reverted by adding salermide, which inhibited TcSir2rp3 expressed in Escherichia coli with a 50% inhibitory concentration (IC50) ± standard error of 1 ± 0.5 μM. We concluded that sirtuin inhibitors targeting TcSir2rp3 could be used in Chagas disease chemotherapy.
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