ArticleNature microbiology2022
Computational identification of a systemic antibiotic for gram-negative bacteria.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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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
73 citing papers in PubMed.
- Total Synthesis and Structural Revision of Rhabdobranin Reveals a Cryptic Gram-Negative Antibiotic.Journal of the American Chemical Society · 2026Article
- Organocatalytic Enantioselective Divergent Synthesis of Pillar[5]Arenes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- L-type pyocins inhibit the BAM complex to kill without cell entry.Nature communications · 2026Article
- A deformylase inhibitor expands therapeutic options for Lyme disease.Research square · 2026Article
- Integration of Membrane Proteins into the Outer Membrane of Diderm Bacteria by the BAM Complex.Chemical reviews · 2026Review
- The BaeSR two-component system activatesmBio · 2026Article
- SET-M33 peptide as a selectiveMicrobiology spectrum · 2026Article
- Reprogrammed SimCells for antimicrobial therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- Discovery of antimicrobial peptides targeting Acinetobacter baumannii via a pre-trained and fine-tuned few-shot learning-based pipeline.Nature communications · 2026Article
- RadicalJournal of the American Chemical Society · 2026Article
- Asymmetric envelope surface disposition of secreted protein YjbI controls bimodal antibiotic susceptibilities in C. crescentus.The EMBO journal · 2026Article
- Loss of DNA mismatch repair genes leads to acquisition of antibiotic resistance independent of secondary mutations.PLoS genetics · 2026Article
- S9 protease WprPCommunications chemistry · 2026Article
- Targeting Bacterial Cell Wall Synthesis: Structural Insights and Emerging Therapeutic Strategies.Pharmaceutics · 2026Review
- P450 Cyptide Synthase KwwB Catalyzes Trp-C5-Trp-N1 Cross-Linking and Accepts Diverse Precursor Peptides.Organic letters · 2026Article
- Protein-Protein Interactions as Promising Molecular Targets for Novel Antimicrobials Aimed at Gram-Negative Bacteria.International journal of molecular sciences · 2025Review
- A novel homoarginine-containing cyclic peptide pioamide with selective antipseudomonal activity isolated from the nematode symbiontApplied and environmental microbiology · 2025Article
- Beyond the Resistome: Molecular Insights, Emerging Therapies, and Environmental Drivers of Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2025Review
13 more citing papers are in PubMed but not listed here.
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25 authors.
Funding
Abstract
Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its β-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development.
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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.