ArticlePloS one2011
Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 74 citations in OpenAlex.
- Type VIIb secretion systems in Lactobacillales: insights from streptococci and enterococci.Journal of bacteriology · 2026Review
- Structural and Biophysical Characterization of the Yersinia Type Three Secretion System ATPase YscN.Proteins · 2026Article
- Targeting Undruggable Protein Interactions with DNA Aptamers: Inhibition of the Interaction BetweenInternational journal of molecular sciences · 2026Article
- Anti-infective compounds forSustainable microbiology · 2026Review
- Type III Secretion System in Intestinal Pathogens and Metabolic Diseases.Journal of diabetes research · 2024Review
- Sex differences in immune protection in mice conferred by heterologous vaccines for pneumonic plague.Frontiers in immunology · 2024Article
- Article
- Primary architecture and energy requirements of Type III and Type IV secretion systems.Frontiers in cellular and infection microbiology · 2023Review
- Research Progress on Small Molecular Inhibitors of the Type 3 Secretion System.Molecules (Basel, Switzerland) · 2022Review
- Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems.Frontiers in cellular and infection microbiology · 2022Review
- Novel Disk Diffusion Assay on Magnesium Oxalate Agar To Evaluate the Susceptibility of Yersinia pestis to Type III Secretion System Inhibitors.Microbiology spectrum · 2021Article
- Type 3 secretion system 1 of Salmonella typhimurium and its inhibitors: a novel strategy to combat salmonellosis.Environmental science and pollution research international · 2021Review
- Metallacarborane Derivatives Effective againstInternational journal of molecular sciences · 2021Article
- Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens.Biomolecules · 2021Review
- Molecular Targets and Strategies for Inhibition of the Bacterial Type III Secretion System (T3SS); Inhibitors Directly Binding to T3SS Components.Biomolecules · 2021Review
- Protection Elicited by Attenuated LiveVaccines · 2021Article
- Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs.The Journal of antibiotics · 2021Review
- Novel Noncompetitive Type Three Secretion System ATPase Inhibitors Shut DownBiochemistry · 2020Article
- Animal Models of Type III Secretion System-Mediated Pathogenesis.Pathogens (Basel, Switzerland) · 2019Review
- On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome.MedChemComm · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC(50) values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.
Indexed as
Identifiers
What OpenQuestion holds
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.