ArticleAntimicrobial agents and chemotherapy2013
Inhibitors of eIF2α dephosphorylation slow replication and stabilize latency in Toxoplasma gondii.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review.Parasitology research · 2018Pooled it
- Translational control of Toxoplasma gondii differentiation.Bioscience reports · 2026Review
- The integrated stress response in apicomplexan and trypanosomatid parasites: balancing survival and pathogenesis.Frontiers in immunology · 2026Review
- Review
- Translation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors.Nature communications · 2024Article
- A High-Throughput Amenable Dual Luciferase System for MeasuringAnalytical chemistry · 2023Article
- Advances towards the completeFaculty reviews · 2023Review
- The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii.Nature communications · 2022Article
- A Review of the Biological Activity of Amidrazone Derivatives.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Restriction Checkpoint Controls Bradyzoite Development in Toxoplasma gondii.Microbiology spectrum · 2022Article
- The determinants regulatingFrontiers in microbiology · 2022Review
- Rebound of cyst number following discontinuation of guanabenz treatment for latent toxoplasmosis.Molecular and biochemical parasitology · 2021Article
- The role of upstream open reading frames in translation regulation in the apicomplexan parasitesParasitology · 2021Review
- Host sensing and signal transduction during Toxoplasma stage conversion.Molecular microbiology · 2021Review
- Guanabenz Sensitizes Glioblastoma Cells to Sunitinib by Inhibiting GADD34-Mediated Autophagic Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Efficacy of Guanabenz Combination Therapy against Chronic Toxoplasmosis across Multiple Mouse Strains.Antimicrobial agents and chemotherapy · 2020Article
- Catastrophic consequences: can the feline parasite Toxoplasma gondii prompt the purrfect neuroinflammatory storm following traumatic brain injury?Journal of neuroinflammation · 2020Review
- The molecular biology and immune control of chronic Toxoplasma gondii infection.The Journal of clinical investigation · 2020Review
- The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis.Pathogens (Basel, Switzerland) · 2020Review
- Protozoan persister-like cells and drug treatment failure.Nature reviews. Microbiology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Toxoplasma gondii is an obligate intracellular parasite that permanently infects warm-blooded vertebrates through its ability to convert into a latent tissue cyst form. The latent form (bradyzoite) can reinitiate a life-threatening acute infection if host immunity wanes, most commonly in AIDS or organ transplant patients. We have previously shown that bradyzoite development is accompanied by phosphorylation of the parasite eukaryotic initiation factor 2 alpha subunit (eIF2α), which dampens global protein synthesis and reprograms gene expression. In this study, we analyzed the activities of two specific inhibitors of eIF2α dephosphorylation, salubrinal (SAL) and guanabenz (GA). We establish that these drugs are able to inhibit the dephosphorylation of Toxoplasma eIF2α. Our results show that SAL and GA reduce tachyzoite replication in vitro and in vivo. Furthermore, both drugs induce bradyzoite formation and inhibit the reactivation of latent bradyzoites in vitro. To address whether the antiparasitic activities of SAL and GA involve host eIF2α phosphorylation, we infected mutant mouse embryonic fibroblast (MEF) cells incapable of phosphorylating eIF2α, which had no impact on the efficacies of SAL and GA against Toxoplasma infection. Our findings suggest that SAL and GA may serve as potential new drugs for the treatment of acute and chronic toxoplasmosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.