ArticleThe Biochemical journal2021
A pipeline to evaluate inhibitors of the Pseudomonas aeruginosa exotoxin U.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Topical formulation of repurposed FDA-approved compounds inhibits Pseudomonas aeruginosa ExoU and improves corneal infection outcomes.PLoS pathogens · 2026Article
- What We Can Do in Infectious Keratitis, Except for Conventional Antimicrobial-Based Therapies: Major Narrative Review.Health science reports · 2026Article
- High-risk lineages shape the resistome and virulome of multidrug-resistantFrontiers in cellular and infection microbiology · 2026Article
- Structural and functional insights into Pseudomonas aeruginosa's secretion systems 1-6: regulation, role in microbial keratitis and drug targets.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Stable topical application of antimicrobials using plumbing rings in an ex vivo porcine corneal infection model.PloS one · 2025Article
- Genomic Insights into Vietnamese Extended-Spectrum β-Lactamase-9-Producing Extensively Drug-ResistantPathogens (Basel, Switzerland) · 2024Article
- Unravelling bacterial virulence factors in yeast: From identification to the elucidation of their mechanisms of action.Archives of microbiology · 2024Review
- Pseudomonas aeruginosa ExoU-associated virulence in HCT recipients and patients with hematologic malignancies.Blood advances · 2023Article
- Using next generation antimicrobials to target the mechanisms of infection.npj antimicrobials and resistance · 2023Review
- Research Progress on Small Molecular Inhibitors of the Type 3 Secretion System.Molecules (Basel, Switzerland) · 2022Review
- Using Structure-guided Fragment-Based Drug Discovery to TargetFrontiers in molecular biosciences · 2022Review
- Foundational concepts in the biology of bacterial keratitis.Experimental eye research · 2021Review
- Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis.Frontiers in chemistry · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pseudomonas aeruginosa has recently been highlighted by the World Health Organisation (WHO) as a major threat with high priority for the development of new therapies. In severe P. aeruginosa infections, the phospholipase activity of the type 3 secretion system toxin, ExoU, induces lysis of target host cells and results in the poorest clinical outcomes. We have developed an integrated pipeline to evaluate small molecule inhibitors of ExoU in vitro and in cultured cell models, including a disease-relevant corneal epithelial (HCE-T) scratch and infection model using florescence microscopy and cell viability assays. Compounds Pseudolipasin A, compound A and compound B were effective in vitro inhibitors of ExoU and mitigated P. aeruginosa ExoU-dependent cytotoxicity after infection of HCE-T cells at concentrations as low as 0.5 µM. Addition of the antimicrobial moxifloxacin controlled bacterial load, allowing these assays to be extended from 6 h to 24 h. P. aeruginosa remained cytotoxic to HCE-T cells with moxifloxacin, present at the minimal inhibitory concentration for 24 h, but, when used in combination with either Pseudolipasin A, compound A or compound B, a greater amount of viable cells and scratch healing were observed. Thus, our pipeline provides evidence that ExoU inhibitors could be used in combination with certain antimicrobials as a novel means to treat infections due to ExoU producing P. aeruginosa, as well as the means to identify more potent ExoU inhibitors for future therapeutics.
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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.