ArticleInfection and immunity2011
An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation.
Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- Targeting bacterial phosphotransferase system to prevent the dissemination of antibiotic resistance genes.Acta pharmaceutica Sinica. B · 2026Article
- Bacterial type IV secretion systems and spread of antimicrobial resistance: a study of potential inhibitors to T4SS-based resistance spread.Archives of microbiology · 2025Review
- Structural and functional diversity of type IV secretion systems.Nature reviews. Microbiology · 2024Review
- Small Molecule Inhibitors against the Bacterial PathogenCurrent medicinal chemistry · 2024Review
- Protein-Protein Interaction: Bacterial Two Hybrid.Methods in molecular biology (Clifton, N.J.) · 2024Article
- DNA Transport through the Dynamic Type IV Secretion System.Infection and immunity · 2023Review
- Click Triazole as a Linker for Pretargeting Strategies: Synthesis, Docking Investigations, Fluorescence Diagnosis, and Antibacterial Action Studies.Molecules (Basel, Switzerland) · 2023Article
- Article
- Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems.Frontiers in cellular and infection microbiology · 2022Review
- Intracellular Passage Triggers a Molecular Response in Brucella abortus That Increases Its Infectiousness.Infection and immunity · 2021Article
- Type IV secretion systems: Advances in structure, function, and activation.Molecular microbiology · 2021Review
- Bioengineering ofToxins · 2021Review
- Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs.The Journal of antibiotics · 2021Review
- Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes.Microorganisms · 2020Review
- Thanatin Impairs Lipopolysaccharide Transport Complex Assembly by Targeting LptC-LptA Interaction and Decreasing LptA Stability.Frontiers in microbiology · 2020Article
- Inhibiting bacterial secretion systems in the fight against antibiotic resistance.MedChemComm · 2019Review
- Fragment-based screening identifies inhibitors of ATPase activity and of hexamer formation of Cagα from the Helicobacter pylori type IV secretion system.Scientific reports · 2019Article
- Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.FEMS microbiology reviews · 2018Review
- Interaction via the N terminus of the type IV secretion system (T4SS) protein VirB6 with VirB10 is required for VirB2 and VirB5 incorporation into T-pili and for T4SS function.The Journal of biological chemistry · 2018Article
- Type IV secretion in Gram-negative and Gram-positive bacteria.Molecular microbiology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
As bacterial pathogens develop resistance against most currently used antibiotics, novel alternatives for treatment of microbial infectious diseases are urgently needed. Targeting bacterial virulence functions in order to disarm pathogens represents a promising alternative to classical antibiotic therapy. Type IV secretion systems, which are multiprotein complexes in the cell envelope that translocate effectors into host cells, are critical bacterial virulence factors in many pathogens and excellent targets for such "antivirulence" drugs. The VirB8 protein from the mammalian pathogen Brucella was chosen as a specific target, since it is an essential type IV secretion system component, it participates in multiple protein-protein interactions, and it is essential for the assembly of this translocation machinery. The bacterial two-hybrid system was adapted to assay VirB8 interactions, and a high-throughput screen identified specific small-molecule inhibitors. VirB8 interaction inhibitors also reduced the levels of VirB8 and of other VirB proteins, and many of them inhibited virB gene transcription in Brucella abortus 2308, suggesting that targeting of the secretion system has complex regulatory effects in vivo. One compound strongly inhibited the intracellular proliferation of B. abortus 2308 in a J774 macrophage infection model. The results presented here show that in vivo screens with the bacterial two-hybrid assay are suited to the identification of inhibitors of Brucella type IV secretion system function.
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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.