ArticleThe Journal of clinical investigation1995
Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 129 citations in OpenAlex.
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- Characterization of the apicoplast-localized enzymeThe Journal of biological chemistry · 2020Article
- Validation of Putative Apicoplast-Targeting Drugs Using a Chemical Supplementation Assay in Cultured Human Malaria Parasites.Antimicrobial agents and chemotherapy · 2018Article
- rRNA Binding Sites and the Molecular Mechanism of Action of the Tetracyclines.Antimicrobial agents and chemotherapy · 2016Review
- Translational control in Plasmodium and toxoplasma parasites.Eukaryotic cell · 2013Review
- The obligate intracellular parasite Toxoplasma gondii secretes a soluble phosphatidylserine decarboxylase.The Journal of biological chemistry · 2012Article
- The motility of a human parasite, Toxoplasma gondii, is regulated by a novel lysine methyltransferase.PLoS pathogens · 2011Article
- RNA granules present only in extracellular toxoplasma gondii increase parasite viability.International journal of biological sciences · 2011Article
- Identification of potential apicoplast associated therapeutic targets in human and animal pathogen Toxoplasma gondii ME49.Bioinformation · 2011Article
- Evaluation of drug effects on Toxoplasma gondii nuclear and plastid DNA replication using real-time PCR.Parasitology research · 2010Article
- Host cell egress and invasion induce marked relocations of glycolytic enzymes in Toxoplasma gondii tachyzoites.PLoS pathogens · 2008Article
- Multiple antibiotics exert delayed effects against the Plasmodium falciparum apicoplast.Antimicrobial agents and chemotherapy · 2007Article
- Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria.Nucleic acids research · 2007Article
- Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococcus multilocularis.Antimicrobial agents and chemotherapy · 2005Article
- Multiple functionally redundant signals mediate targeting to the apicoplast in the apicomplexan parasite Toxoplasma gondii.Eukaryotic cell · 2004Article
- High-throughput growth assay for Toxoplasma gondii using yellow fluorescent protein.Antimicrobial agents and chemotherapy · 2003Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
We investigated potential targets for the activity of protein synthesis inhibitors against the protozoan parasite Toxoplasma gondii. Although nanomolar concentrations of azithromycin and clindamycin prevent replication of T. gondii in both cell culture and in vivo assays, no inhibition of protein labeling was observed in either extracellular or intracellular parasites treated with up to 100 microM drug for up to 24 h. Quantitative analysis of > 300 individual spots on two-dimensional gels revealed no proteins selectively depleted by 100 microM azithromycin. In contrast, cycloheximide inhibited protein synthesis in a dose-dependent manner. Nucleotide sequence analysis of the peptidyl transferase region from genes encoding the large subunit of the parasite's ribosomal RNA predict that the cytoplasmic ribosomes of T. gondii, like other eukaryotic ribosomes, should be resistant to macrolide antibiotics. Combining cycloheximide treatment with two-dimensional gel analysis revealed a small subset of parasite proteins likely to be synthesized on mitochondrial ribosomes. Synthesis of these proteins was inhibited by 100 microM tetracycline, but not by 100 microM azithromycin or clindamycin. Ribosomal DNA sequences believed to be derived from the T. gondii mitochondrial genome predict macrolide/lincosamide resistance. PCR amplification of total T. gondii DNA identified an additional class of prokaryotic-type ribosomal genes, similar to the plastid-like ribosomal genes of the Plasmodium falciparum. Ribosomes encoded by these genes are predicted to be sensitive to the lincosamide/macrolide class of antibiotics, and may serve as the functional target for azithromycin, clindamycin, and other protein synthesis inhibitors in Toxoplasma and related parasites.
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