Trial reportPLoS pathogens2014
Cationic antimicrobial peptides promote microbial mutagenesis and pathoadaptation in chronic infections.
Trial report in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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.
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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Molecular exploration of host-pathogen interactions in severeFrontiers in medicine · 2025Pooled it
- Mutations in the mucA gene of Pseudomonas aeruginosa promote disease exacerbation.Archives of microbiology · 2026Review
- Feeding the invaders: how metabolic imbalance shapes infection and biofilm development.FEMS microbiology reviews · 2026Review
- Cathelicidins: Opportunities and Challenges in Skin Therapeutics and Clinical Translation.Antibiotics (Basel, Switzerland) · 2024Review
- Antimicrobial Peptides and Small Molecules Targeting the Cell Membrane of Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2023Review
- Membrane Potential-Dependent Uptake of Cationic Oligoimidazolium Mediates Bacterial DNA Damage and Death.Antimicrobial agents and chemotherapy · 2023Article
- Airway mucus in pulmonary diseases: Muco-adhesive and muco-penetrating particles to overcome the airway mucus barriers.International journal of pharmaceutics · 2023Review
- Biofilm Lifestyle in Recurrent Urinary Tract Infections.Life (Basel, Switzerland) · 2023Review
- Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2022Article
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
- The Neisseria gonorrhoeae type IV pilus promotes resistance to hydrogen peroxide- and LL-37-mediated killing by modulating the availability of intracellular, labile iron.PLoS pathogens · 2022Article
- Biofilm aggregates and the host airway-microbial interface.Frontiers in cellular and infection microbiology · 2022Review
- Multiple roles of ribosomal antimicrobial peptides in tackling global antimicrobial resistance.Royal Society open science · 2022Article
- Machine Learning Prediction of Antimicrobial Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Treatment ofFrontiers in microbiology · 2022Review
- A study on fungal defensin against multidrug-resistant Clostridium perfringens and its treatment on infected poultry.Applied microbiology and biotechnology · 2021Article
- BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression.Scientific reports · 2021Article
- The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent.Antibiotics (Basel, Switzerland) · 2021Review
- UPR modulation of host immunity by Pseudomonas aeruginosa in cystic fibrosis.Clinical science (London, England : 1979) · 2020Article
- Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms.Frontiers in medical technology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Acquisition of adaptive mutations is essential for microbial persistence during chronic infections. This is particularly evident during chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients. Thus far, mutagenesis has been attributed to the generation of reactive species by polymorphonucleocytes (PMN) and antibiotic treatment. However, our current studies of mutagenesis leading to P. aeruginosa mucoid conversion have revealed a potential new mutagen. Our findings confirmed the current view that reactive oxygen species can promote mucoidy in vitro, but revealed PMNs are proficient at inducing mucoid conversion in the absence of an oxidative burst. This led to the discovery that cationic antimicrobial peptides can be mutagenic and promote mucoidy. Of specific interest was the human cathelicidin LL-37, canonically known to disrupt bacterial membranes leading to cell death. An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy and to promote rifampin resistance in both P. aeruginosa and Escherichia coli. The mechanism of mutagenesis was found to be dependent upon sub-inhibitory concentrations of LL-37 entering the bacterial cytosol and binding to DNA. LL-37/DNA interactions then promote translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations. A model of LL-37 bound to DNA was generated, which reveals amino termini α-helices of dimerized LL-37 bind the major groove of DNA, with numerous DNA contacts made by LL-37 basic residues. This demonstrates a mutagenic role for antimicrobials previously thought to be insusceptible to resistance by mutation, highlighting a need to further investigate their role in evolution and pathoadaptation in chronic 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.