ArticleProceedings of the National Academy of Sciences of the United States of America2012
Molecular target validation, antimicrobial delivery, and potential treatment of Toxoplasma gondii infections.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed.
- Evaluation of the efficicacy of myrcene in the treatment of Eimeria tenella and Toxoplasma gondii infection.The Journal of veterinary medical science · 2025Article
- Zinc Oxide and Magnesium-Doped Zinc Oxide Nanoparticles Ameliorate Murine Chronic Toxoplasmosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- TZD-Based Hybrid Molecules Act as Dual Anti-International journal of molecular sciences · 2023Article
- Inhibition ofJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview.Current pediatrics reports · 2022Review
- Building Programs to Eradicate Toxoplasmosis Part IV: Understanding and Development of Public Health Strategies and Advances "Take a Village".Current pediatrics reports · 2022Review
- Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases.Molecules (Basel, Switzerland) · 2021Review
- Application of Dendrimers for Treating Parasitic Diseases.Pharmaceutics · 2021Review
- Curcumin@metal organic frameworks nano-composite for treatment of chronic toxoplasmosis.Journal of materials science. Materials in medicine · 2020Article
- Treatment of toxoplasmosis: Current options and future perspectives.Food and waterborne parasitology · 2019Review
- ApiAP2 Transcription Factors in Apicomplexan Parasites.Pathogens (Basel, Switzerland) · 2019Review
- A New Antisense Phosphoryl Guanidine Oligo-2'-O-Methylribonucleotide Penetrates Into Intracellular Mycobacteria and Suppresses Target Gene Expression.Frontiers in pharmacology · 2019Article
- Application of Dendrimers for the Treatment of Infectious Diseases.Molecules (Basel, Switzerland) · 2018Review
- CSGID Solves Structures and Identifies Phenotypes for Five Enzymes inFrontiers in cellular and infection microbiology · 2018Article
- Targeted gene knockdown validates the essential role of lactate dehydrogenase in Cryptosporidium parvum.International journal for parasitology · 2017Article
- Inhibition of Pseudomonas aeruginosa by Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers.Antimicrobial agents and chemotherapy · 2017Article
- Article
- Drugs in development for toxoplasmosis: advances, challenges, and current status.Drug design, development and therapy · 2017Review
- A Systematic Review ofFrontiers in microbiology · 2017Review
- Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Toxoplasma gondii persistently infects over two billion people worldwide. It can cause substantial morbidity and mortality. Existing treatments have associated toxicities and hypersensitivity and do not eliminate encysted bradyzoites that recrudesce. New, improved medicines are needed. Transductive peptides carry small molecule cargos across multiple membranes to enter intracellular tachyzoites and encysted bradyzoites. They also carry cargos into retina when applied topically to eyes, and cross blood brain barrier when administered intravenously. Phosphorodiamidate morpholino oligomers (PMO) inhibit gene expression in a sequence-specific manner. Herein, effect of transductive peptide conjugated PMO (PPMO) on tachyzoite protein expression and replication in vitro and in vivo was studied. Initially, sequence-specific PPMO successfully reduced transfected T. gondii's fluorescence and luminescence. PPMO directed against T. gondii's dihydrofolate reductase (DHFR), an enzyme necessary for folate synthesis, limited tachyzoite replication. Rescue with exogenous folate demonstrated DHFR PPMO's specificity. PPMO directed against enoyl-ACP reductase (ENR), an enzyme of type II fatty acid synthesis that is structurally distinct in T. gondii from ENR in mammalian cells was investigated. PPMO directed against plant-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was characterized. ENR and AP2XI-3 PPMO each restricted intracellular parasite replication validating these molecular targets in tachyzoites. DHFR-specific PPMO administered to infected mice diminished parasite burden. Thus, these antisense oligomers are a versatile approach to validate T. gondii molecular targets, reduce essential T. gondii proteins in vitro and in vivo, and have potential for development as curative medicines.
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