ArticleCell host & microbe2012
Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin.
Article in Cell host & microbe, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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124 citing papers in PubMed, 236 citations in OpenAlex.
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- Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.Cell chemical biology · 2025Article
- Design and Development of Lysyl tRNA Synthetase Inhibitors, for the Treatment of Tuberculosis.Journal of medicinal chemistry · 2025Article
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- Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.Communications biology · 2024Article
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- Genetic crosses within and between species ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Targeting antimalarial metabolites from the actinomycetes associated with the Red Sea sponge Callyspongia siphonella using a metabolomic method.BMC microbiology · 2023Article
- New Cyclopiane Diterpenes and Polyketide Derivatives from Marine Sediment-Derived FungusMarine drugs · 2023Article
64 more citing papers are in PubMed but not listed here.
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25 authors at 4 institutions in 3 countries.
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Abstract
With renewed calls for malaria eradication, next-generation antimalarials need be active against drug-resistant parasites and efficacious against both liver- and blood-stage infections. We screened a natural product library to identify inhibitors of Plasmodium falciparum blood- and liver-stage proliferation. Cladosporin, a fungal secondary metabolite whose target and mechanism of action are not known for any species, was identified as having potent, nanomolar, antiparasitic activity against both blood and liver stages. Using postgenomic methods, including a yeast deletion strains collection, we show that cladosporin specifically inhibits protein synthesis by directly targeting P. falciparum cytosolic lysyl-tRNA synthetase. Further, cladosporin is >100-fold more potent against parasite lysyl-tRNA synthetase relative to the human enzyme, which is conferred by the identity of two amino acids within the enzyme active site. Our data indicate that lysyl-tRNA synthetase is an attractive, druggable, antimalarial target that can be selectively inhibited.
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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.