ArticleMolecular microbiology2019
Inhibition of autotransporter biogenesis by small molecules.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Protein-Protein Interactions as Promising Molecular Targets for Novel Antimicrobials Aimed at Gram-Negative Bacteria.International journal of molecular sciences · 2025Review
- An Rcs Stress-Based High-Throughput Screen Reveals Novel Gyrase Inhibitors as Indirect Inducers of Cell Envelope Stress in Gram-Negative Bacteria.ACS infectious diseases · 2025Article
- Antibacterial macrocyclic peptides reveal a distinct mode of BamA inhibition.Nature communications · 2025Article
- Overproduction of β-barrel outer membrane proteins inExtracellular vesicles and circulating nucleic acids · 2025Article
- Article
- ATP-independent assembly machinery of bacterial outer membranes: BAM complex structure and function set the stage for next-generation therapeutics.Protein science : a publication of the Protein Society · 2024Review
- Stress-Based Screening for Compounds That Inhibit β-Barrel Outer Membrane Protein Assembly in Gram-Negative Bacteria.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Sensing of Antibiotic-Bacteria Interactions.Antibiotics (Basel, Switzerland) · 2023Review
- Surveying membrane landscapes: a new look at the bacterial cell surface.Nature reviews. Microbiology · 2023Review
- β-Barrel Assembly Machinery (BAM) Complex as Novel Antibacterial Drug Target.Molecules (Basel, Switzerland) · 2023Review
- Targeting BAM for Novel Therapeutics against Pathogenic Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- Phosphatidylglycerol Is the Lipid Donor for Synthesis of Phospholipid-Linked Enterobacterial Common Antigen.Journal of bacteriology · 2023Article
- Synthesis and Structure-Activity Studies of β-Barrel Assembly Machine Complex Inhibitor MRL-494.ACS infectious diseases · 2022Article
- Optimising expression of the large dynamic range FRET pair mNeonGreen and superfolder mTurquoise2Scientific reports · 2022Article
- Microscale communication between bacterial pathogens and the host epithelium.Genes and immunity · 2021Review
- Overproducing the BAM complex improves secretion of difficult-to-secrete recombinant autotransporter chimeras.Microbial cell factories · 2021Article
- Combining Cell Envelope Stress Reporter Assays in a Screening Approach to Identify BAM Complex Inhibitors.ACS infectious diseases · 2021Article
- Eeyarestatin 24 impairs SecYEG-dependent protein trafficking and inhibits growth of clinically relevant pathogens.Molecular microbiology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disarming pathogens by targeting virulence factors is a promising alternative to classic antibiotics. Many virulence factors in Gram-negative bacteria are secreted via the autotransporter (AT) pathway, also known as Type 5 secretion. These factors are secreted with the assistance of two membrane-based protein complexes: Sec and Bam. To identify inhibitors of the AT pathway, we used transcriptomics analysis to develop a fluorescence-based high-throughput assay that reports on the stress induced by the model AT hemoglobin protease (Hbp) when its secretion across the outer membrane is inhibited. Screening a library of 1600 fragments yielded the compound VUF15259 that provokes cell envelope stress and secretion inhibition of the ATs Hbp and Antigen-43. VUF15259 also impairs β-barrel folding activity of various outer membrane proteins. Furthermore, we found that mutants that are compromised in outer membrane protein biogenesis are more susceptible to VUF15259. Finally, VUF15259 induces the release of vesicles that appear to assemble in short chains. Taken together, VUF15259 is the first reported compound that inhibits AT secretion and our data are mostly consistent with VUF15259 interfering with the Bam-complex as potential mode of action. The validation of the presented assay incites its use to screen larger compound libraries with drug-like compounds.
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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.