ArticleClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2018
Enhanced efficacy of the engineered antimicrobial peptide WLBU2 via direct airway delivery in a murine model of Pseudomonas aeruginosa pneumonia.
Article in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 48 citations in OpenAlex.
- Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence.Antimicrobial agents and chemotherapy · 2025Review
- In Vitro and In Vivo Antibacterial and Antibiofilm Activity of Zinc Sulfate (ZnSOAntibiotics (Basel, Switzerland) · 2025Article
- Esc peptides and derivatives potentiate the activity of CFTR with gating defects and display antipseudomonal activity in cystic fibrosis-like lung disease.Cellular and molecular life sciences : CMLS · 2025Article
- Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.Signal transduction and targeted therapy · 2025Review
- Recreating chronic respiratory infectionsEuropean respiratory review : an official journal of the European Respiratory Society · 2024Review
- New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis.Antibiotics (Basel, Switzerland) · 2024Review
- In vitro and in vivo antibiofilm activity of the synthetic antimicrobial peptide WLBU2 against multiple drug resistant Pseudomonas aeruginosa strains.BMC microbiology · 2023Article
- Advances of Antimicrobial Peptide-Based Biomaterials for the Treatment of Bacterial Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Antimicrobial Peptide Mechanism Studied by Scattering-Guided Molecular Dynamics Simulation.The journal of physical chemistry. B · 2022Article
- WLBU2 Antimicrobial Peptide as a Potential Therapeutic for Treatment of Resistant BacterialTurkish journal of pharmaceutical sciences · 2022Article
- Evolved resistance to a novel cationic peptide antibiotic requires high mutation supply.Evolution, medicine, and public health · 2022Article
- Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents.Frontiers in microbiology · 2022Review
- Antibiofilm activity of host defence peptides: complexity provides opportunities.Nature reviews. Microbiology · 2021Review
- Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era.Acta pharmaceutica Sinica. B · 2021Review
- Synergism between WLBU2 peptide and antibiotics against methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacter cloacae.Journal of applied biomedicine · 2021Article
- Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice.Current reviews in clinical and experimental pharmacology · 2021Article
- The Long-Term Effect of a Nine Amino-Acid Antimicrobial Peptide AS-hepc3Frontiers in cellular and infection microbiology · 2021Article
- Evaluation of Peptide-Based Probes towardACS infectious diseases · 2020Article
- Article
- Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectivesPseudomonas aeruginosa is a common cause of pneumonia in patients with cystic fibrosis with the property to generate multidrug resistance against clinically used antibiotics. Antimicrobial peptides (AMPs) are a diverse group of effector molecules of the innate immune system that protect the host against pathogens. However, the lack of activity in common biological matrices has hampered efforts towards clinical development. In this study, we evaluated the therapeutic potential of the engineered AMP WLBU2 via direct airway delivery in a murine model of P. aeruginosa infection.
methodsThe human AMPs LL37 and WLBU2 were compared for (i) antibiofilm activity using P. aeruginosa on polarized human bronchial epithelial cells, and (ii) efficacy in P. aeruginosa pneumonia in mice using intratracheal instillation of bacteria and AMPs.
resultsWLBU2 (16 μM) prevents biofilm formation by up to 3-log compared with 1-log reduction by LL37. With a single dose of 1 μg (0.05 mg/kg) delivered intratracheally, the initial effect of LL37 was moderate and transitory, as bacterial load and inflammatory cytokines increased at 24 h with observed signs of disease such as lethargy and hypothermia, consistent with moribund state requiring euthanasia. In sharp contrast, WLBU2 reduced bacterial burden (by 2 logs) and bacteria-induced inflammation (leucocytic infiltrates, cytokine and chemokine gene expression) at 6 h and 24 h post-exposure, with no observed signs of disease or host toxicity.
conclusionThese promising results now establish a much lower minimum therapeutic dose of WLBU2 (a net gain of 80-fold) compared with the previously reported 4 mg/kg systemic minimum therapeutic dose, with significant implications for clinical development.
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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 Socratic graph.