ArticleJournal of the American Chemical Society2019
Small Molecule Inhibitors of the BfrB-Bfd Interaction Decrease Pseudomonas aeruginosa Fitness and Potentiate Fluoroquinolone Activity.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 20 citations in OpenAlex.
- Inhibiting Bacterioferritin Iron Release Induces Iron Starvation and Metabolic Downshift, Potentiating Aminoglycosides inACS infectious diseases · 2026Article
- Biological and clinical significance of iron inJournal of bacteriology · 2026Review
- Structural Analysis and Inhibitor Modeling of Bacterioferritin From Brucella abortus.Proteins · 2026Article
- Single-bacterial cell insights into mechanisms of ceftriaxone resistance in Neisseria subflava.Nature communications · 2026Article
- Porphyrin pathways as targets for combating antimicrobial resistance: virulence and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Inhibitors of the Bacterioferritin Ferredoxin Complex Dysregulate Iron Homeostasis and KillACS infectious diseases · 2025Article
- Molybdate uptake interplay with ROS tolerance modulates bacterial pathogenesis.Science advances · 2025Article
- A Closer Look at the FeS Heme Bonds in Azotobacter vinelandii Bacterioferritin: QM/MM and Local Mode Analysis.Journal of computational chemistry · 2025Article
- The crystal structure of Acinetobacter baumannii bacterioferritin reveals a heteropolymer of bacterioferritin and ferritin subunits.Scientific reports · 2024Article
- Article
- Mobilization of iron stored in bacterioferritin, a new target for perturbing iron homeostasis and developing antibacterial and antibiofilm molecules.Journal of inorganic biochemistry · 2023Review
- Synthesis of Chiral Tricyclic Pyrone Molecules via Palladium(0)-Catalyzed Displacement Reactions of Chiral Tricyclic Pyrone Acetate With Azide or Amine.ChemistrySelect · 2023Article
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- Efficient One-Pot Synthesis of Novel Caffeic Acid Derivatives as Potential Antimalarials.Journal of parasitology research · 2023Article
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- Flavin-mediated reductive iron mobilization from frog M and Mycobacterial ferritins: impact of their size, charge and reactivities with NADH/OJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Electron Transfer from Haem to the Di-Iron Ferroxidase Centre in Bacterioferritin.Angewandte Chemie (International ed. in English) · 2021Article
- Electron Transfer from Haem to the Di-Iron Ferroxidase Centre in Bacterioferritin.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Iron Oxidation inAngewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Iron Oxidation in Escherichia coli Bacterioferritin Ferroxidase Centre, a Site Designed to React Rapidly with HAngewandte Chemie (International ed. in English) · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The iron storage protein bacterioferritin (BfrB) is central to bacterial iron homeostasis. The mobilization of iron from BfrB, which requires binding by a cognate ferredoxin (Bfd), is essential to the regulation of cytosolic iron levels in P. aeruginosa. This paper describes the structure-guided development of small molecule inhibitors of the BfrB-Bfd protein-protein interaction. The process was initiated by screening a fragment library and followed by obtaining the structure of a fragment hit bound to BfrB. The structural insights were used to develop a series of 4-(benzylamino)- and 4-((3-phenylpropyl)amino)-isoindoline-1,3-dione analogs that selectively bind BfrB at the Bfd binding site. Challenging P. aeruginosa cells with the 4-substituted isoindoline analogs revealed a dose-dependent growth phenotype. Further investigation determined that the analogs elicit a pyoverdin hyperproduction phenotype that is consistent with blockade of the BfrB-Bfd interaction and ensuing irreversible accumulation of iron in BfrB, with concomitant depletion of iron in the cytosol. The irreversible accumulation of iron in BfrB prompted by the 4-substituted isoindoline analogs was confirmed by visualization of BfrB-iron in P. aeruginosa cell lysates separated on native PAGE gels and stained for iron with Ferene S. Challenging P. aeruginosa cultures with a combination of commercial fluoroquinolone and our isoindoline analogs results in significantly lower cell survival relative to treatment with either antibiotic or analog alone. Collectively, these findings furnish proof of concept for the usefulness of small molecule probes designed to dysregulate bacterial iron homeostasis by targeting a protein-protein interaction pivotal for iron storage in the bacterial cell.
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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.