ArticlePLoS neglected tropical diseases2011
Genetic reconstruction of protozoan rRNA decoding sites provides a rationale for paromomycin activity against Leishmania and Trypanosoma.
Article in PLoS neglected tropical diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence.Pathogens (Basel, Switzerland) · 2026Pooled it
- World Association for Veterinary Dermatology Consensus Statement for Diagnosis, and Evidence-Based Clinical Practice Guidelines for Treatment and Prevention of Canine Leishmaniosis.Veterinary dermatology · 2025Guideline
- Identification of Novel Flavonoids and Ansa-Macrolides with Activities againstPathogens (Basel, Switzerland) · 2024Article
- Structure-Activity Relationships for 5'' Modifications of 4,5-Aminoglycoside Antibiotics.ChemMedChem · 2022Article
- Experimental Selection of Paromomycin Resistance inMicroorganisms · 2021Article
- Identification ofMicroorganisms · 2021Article
- Apralogs: Apramycin 5-Journal of the American Chemical Society · 2020Article
- Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.ACS infectious diseases · 2019Article
- Aminoglycoside interactions and impacts on the eukaryotic ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin.Nature communications · 2017Article
- Crystal structure of eukaryotic ribosome and its complexes with inhibitors.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes.Nature communications · 2016Article
- Structural basis for selective targeting of leishmanial ribosomes: aminoglycoside derivatives as promising therapeutics.Nucleic acids research · 2015Article
- Article
- Ubiquitination-mediated interaction among domains is responsible for inhibition of RNA endonuclease activity of mRNA cycling sequence binding protein from L. donovani (LdCSBP).Parasitology research · 2014Article
- New trends in aminoglycosides use.MedChemComm · 2014Article
- 4'-O-substitutions determine selectivity of aminoglycoside antibiotics.Nature communications · 2014Article
- Identification of the molecular attributes required for aminoglycoside activity against Leishmania.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycoside antibiotics target the ribosomal decoding A-site and are active against a broad spectrum of bacteria. These compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16S rRNA. One particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by Leishmania spp. The precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic and/or the mitochondrial protozoan ribosome. To establish an experimental model for the study of protozoan decoding-site function, we constructed bacterial chimeric ribosomes where the central part of bacterial 16S rRNA helix 44 has been replaced by the corresponding Leishmania and Trypanosoma rRNA sequences. Relating the results from in-vitro ribosomal assays to that of in-vivo aminoglycoside activity against Trypanosoma brucei, as assessed in cell cultures and in a mouse model of infection, we conclude that aminoglycosides affect cytosolic translation while the mitochondrial ribosome of trypanosomes is not a target for aminoglycoside antibiotics.
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