ArticleNature communications2021
trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 45 citations in OpenAlex.
- The regulation of AsfR on tmRNA expression mediates bacterial motility and virulence inVirulence · 2026Article
- Ribosomal protein bL27 protects translating ribosomes from tmRNA-SmpB.Science advances · 2026Article
- Article
- US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institutes of Health Co-Sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Article
- Ribosomal Protein bL27 Protects Translating Ribosomes from tmRNA-SmpB.bioRxiv : the preprint server for biology · 2026Article
- Antibiotic-Adjuvants Abolish Resistance Conferred by theACS infectious diseases · 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
- The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant Neisseria gonorrhoeae infection in vivo.Nature communications · 2025Article
- An RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting.Nature communications · 2025Article
- Global health perspectives on antibacterial drug discovery and the preclinical pipeline.Nature reviews. Microbiology · 2025Review
- AACS infectious diseases · 2025Article
- An integrated proteo-transcriptomics approach reveals novel drug targets against multidrug resistantFrontiers in microbiology · 2025Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- RqcH supports survival in the absence of non-stop ribosome rescue factors.bioRxiv : the preprint server for biology · 2024Article
- 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
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Success stories of natural product-derived compounds from plants as multidrug resistance modulators in microorganisms.RSC advances · 2023Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.
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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.