ArticleProceedings of the National Academy of Sciences of the United States of America2013
Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The trial behind it
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
58 citing papers in PubMed, 94 citations in OpenAlex.
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- Blocked transcription-translation complexes are rescued by transcript release followed byJournal of bacteriology · 2026Article
- Ribosomal protein bL27 protects translating ribosomes from tmRNA-SmpB.Science advances · 2026Article
- Deep learning-enabled discovery of antibiotics effective againstScience translational medicine · 2026Article
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- Ribosomal Protein bL27 Protects Translating Ribosomes from tmRNA-SmpB.bioRxiv : the preprint server for biology · 2026Article
- Halogenated N-(1,3,4-oxadiazol-2-yl) benzamides are effective eradicators of methicillin-resistant Staphylococcus aureus biofilms.Bioorganic & medicinal chemistry · 2026Article
- A cascade of structural rearrangements positions peptide release factor 2 for polypeptide hydrolysis on the ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of KKL-35 as a Novel Carnosine Dipeptidase 2 (CNDP2) Inhibitor by In Silico Screening.Molecules (Basel, Switzerland) · 2025Article
- AJournal of bacteriology · 2025Article
- AACS infectious diseases · 2025Article
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- KKL-35 inhibits growth of Staphylococcus aureus by systematically changing bacterial phenotypes.Archives of microbiology · 2024Article
- The Structural and Molecular Mechanisms ofMolecules (Basel, Switzerland) · 2024Review
- Enhancing bactericidal activities of ciprofloxacin by targeting the trans-translation system that is involved in stress responses in Klebsiella pneumoniae.Archives of microbiology · 2024Article
- Substitution of Glu378 in EF-Tu disrupts binding to KKL-55.microPublication biology · 2024Article
- Improved Antibacterial Activity of 1,3,4-Oxadiazole-Based Compounds That RestrictACS infectious diseases · 2023Article
- How hydrolytic exoribonucleases impact human disease: Two sides of the same story.FEBS open bio · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The trans-translation pathway for protein tagging and ribosome release plays a critical role for viability and virulence in a wide range of pathogens but is not found in animals. To explore the use of trans-translation as a target for antibiotic development, a high-throughput screen and secondary screening assays were used to identify small molecule inhibitors of the pathway. Compounds that inhibited protein tagging and proteolysis of tagged proteins were recovered from the screen. One of the most active compounds, KKL-35, inhibited the trans-translation tagging reaction with an IC50 = 0.9 µM. KKL-35 and other compounds identified in the screen exhibited broad-spectrum antibiotic activity, validating trans-translation as a target for drug development. This unique target could play a key role in combating strains of pathogenic bacteria that are resistant to existing antibiotics.
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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.