ArticleNature communications2022
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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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
25 citing papers in PubMed, 43 citations in OpenAlex.
- Dual-engineering metalloimmunotherapy mediatesBioactive materials · 2026Article
- Multimodal computational discovery of MvfR inhibitors targeting quorum sensing in multi-drug-resistant Pseudomonas aeruginosa.Scientific reports · 2026Article
- Glycerol monolaurate attenuates necrotic enteritis in broilers by improving gut-liver health and remodeling the gut microbiota.Journal of animal science and biotechnology · 2026Article
- A novel approach to combatMicrobiology spectrum · 2026Article
- Genomic and epidemiological identification of Pseudomonas aeruginosa transmission chains and in hospital ICUs.Genome biology · 2026Article
- Article
- Broadly Defined Antibiotic Adjuvants forThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Multidrug-resistantVirulence · 2025Review
- Anti-QS Strategies AgainstMicroorganisms · 2025Review
- Advancements and Challenges in Modeling Mechanobiology in Intestinal Host-Microbiota Interaction.ACS applied materials & interfaces · 2025Review
- MvfR ShapesCells · 2025Article
- The role of programmed cell death in organ dysfunction induced by opportunistic pathogens.Critical care (London, England) · 2025Review
- Dual RNA sequencing of a co-culture model of Pseudomonas aeruginosa and human 2D upper airway organoids.Scientific reports · 2025Article
- Quorum Sensing and its Inhibition inCurrent drug targets · 2025Review
- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- Revealing the impact ofFrontiers in immunology · 2025Article
- 'Wild Type'.Microbiology (Reading, England) · 2024Review
- Article
- Biofilm-mediated infections by multidrug-resistant microbes: a comprehensive exploration and forward perspectives.Archives of microbiology · 2024Review
- Exploiting the Zebrafish Model for Sepsis Research: Insights into Pathophysiology and Therapeutic Potentials.Drug design, development and therapy · 2024Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
Intestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation. Pseudomonas aeruginosa (PA) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis. PA infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance. Inhibition of the quorum-sensing transcriptional regulator MvfR(PqsR) is a desirable anti-PA anti-virulence strategy as MvfR controls multiple acute and chronic virulence functions. Here we show that MvfR promotes intestinal permeability and report potent anti-MvfR compounds, the N-Aryl Malonamides (NAMs), resulting from extensive structure-activity-relationship studies and thorough assessment of the inhibition of MvfR-controlled virulence functions. This class of anti-virulence non-native ligand-based agents has a half-maximal inhibitory concentration in the nanomolar range and strong target engagement. Using a NAM lead in monotherapy protects murine intestinal barrier function, abolishes MvfR-regulated small molecules, ameliorates bacterial dissemination, and lowers inflammatory cytokines. This study demonstrates the importance of MvfR in PA-driven intestinal permeability. It underscores the utility of anti-MvfR agents in maintaining gut mucosal integrity, which should be part of any successful strategy to prevent/treat PA infections and associated gut-derived sepsis in critical illness settings. NAMs provide for the development of crucial preventive/therapeutic monotherapy options against untreatable MDR PA infections.
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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.