ArticleNature chemical biology2015
Compounds targeting disulfide bond forming enzyme DsbB of Gram-negative bacteria.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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
35 citing papers in PubMed.
- Antibiotic potentiation and inhibition of cross-resistance in pathogens associated with cystic fibrosis.eLife · 2026Article
- Article
- Disulphide bond-forming enzymes in clostridial species.Microbiology (Reading, England) · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Disulfide bonds are required for cell division, cell envelope biogenesis and antibiotic resistance proteins in mycobacteria.bioRxiv : the preprint server for biology · 2025Article
- Development of luciferase-based highly sensitive reporters that detect ER-associated protein biogenesis abnormalities.iScience · 2024Article
- Periplasmic Chaperones: Outer Membrane Biogenesis and Envelope Stress.Annual review of microbiology · 2024Review
- Warfarin analogs target disulfide bond-forming enzymes and suggest a residue important for quinone and coumarin binding.The Journal of biological chemistry · 2024Article
- Cell envelope structural and functional contributions to antibiotic resistance inJournal of bacteriology · 2024Article
- Development of a sensor for disulfide bond formation in diverse bacteria.Journal of bacteriology · 2024Article
- A genetic screen identifies a role for oprF in Pseudomonas aeruginosa biofilm stimulation by subinhibitory antibiotics.NPJ biofilms and microbiomes · 2024Article
- Distinct enzymatic strategies forCritical reviews in biochemistry and molecular biology · 2023Article
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Union Is Strength: Target-Based and Whole-Cell High-Throughput Screens in Antibacterial Discovery.Journal of bacteriology · 2022Review
- Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials.ChemMedChem · 2022Article
- Article
- Smart Flow Electrosynthesis and Application of Organodisulfides in Redox Flow Batteries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Antivirulence DsbA inhibitors attenuateFASEB bioAdvances · 2021Article
- Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021Review
- A high-throughput cell-based assay pipeline for the preclinical development of bacterial DsbA inhibitors as antivirulence therapeutics.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond. These proteins include numerous bacterial virulence factors, and thus bacterial enzymes that promote disulfide bond formation represent targets for compounds inhibiting bacterial virulence. Here, we describe a new target- and cell-based screening methodology for identifying compounds that inhibit the disulfide bond-forming enzymes Escherichia coli DsbB (EcDsbB) or Mycobacterium tuberculosis VKOR (MtbVKOR), which can replace EcDsbB, although the two are not homologs. Initial screening of 51,487 compounds yielded six specifically inhibiting EcDsbB. These compounds share a structural motif and do not inhibit MtbVKOR. A medicinal chemistry approach led us to select related compounds, some of which are much more effective DsbB inhibitors than those found in the screen. These compounds inhibit purified DsbB and prevent anaerobic growth of E. coli. Furthermore, these compounds inhibit all but one of the DsbBs of nine other Gram-negative pathogenic bacteria tested.
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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.