ArticlePloS one2015
Evidence for a novel mechanism of antimicrobial action of a cyclic R-,W-rich hexapeptide.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed.
- Strong Membrane Permeabilization Activity Can Reduce Selectivity of Cyclic Antimicrobial Peptides.The journal of physical chemistry. B · 2025Article
- The Functional Mechanism and Structure-Activity Relationship of Antibacterial Peptides.Current topics in medicinal chemistry · 2025Review
- Lipid phase separation impairs membrane thickness sensing by theMicrobiology spectrum · 2024Article
- Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents.Pharmaceutics · 2024Article
- Bactericidal Activity toAntibiotics (Basel, Switzerland) · 2023Article
- Structure-activity relationships of antibacterial peptides.Microbial biotechnology · 2023Review
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Harnessing the Role of Bacterial Plasma Membrane Modifications for the Development of Sustainable Membranotropic Phytotherapeutics.Membranes · 2022Review
- Where Electrostatics Matter: Bacterial Surface Neutralization and Membrane Disruption by Antimicrobial Peptides SAAP-148 and OP-145.Biomolecules · 2022Article
- Disruption of the Cytoplasmic Membrane Structure and Barrier Function Underlies the Potent Antiseptic Activity of Octenidine in Gram-Positive Bacteria.Applied and environmental microbiology · 2022Article
- Membrane Activity of LL-37 Derived Antimicrobial Peptides againstBiomolecules · 2022Article
- Synergistic Action of Antimicrobial Lung Proteins againstInternational journal of molecular sciences · 2021Article
- Modulatory Effects of Acidic pH and Membrane Potential on the Adsorption of pH-Sensitive Peptides to Anionic Lipid Membrane.Membranes · 2021Article
- Controversy of Peptide Cyclization from Tripeptide.Molecules (Basel, Switzerland) · 2021Article
- Article
- EcDBS1R4, an Antimicrobial Peptide Effective againstInternational journal of molecular sciences · 2020Article
- Resistance of early stationary phase E. coli to membrane permeabilization by the antimicrobial peptide Cecropin A.Biochimica et biophysica acta. Biomembranes · 2019Article
- Tryptophan-Rich and Proline-Rich Antimicrobial Peptides.Molecules (Basel, Switzerland) · 2018Review
- The novel antibiotic rhodomyrtone traps membrane proteins in vesicles with increased fluidity.PLoS pathogens · 2018Article
- Cyclic Peptides as Novel Therapeutic Microbicides: Engineering of Human Defensin Mimetics.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of antimicrobial peptides as new class of antibiotic agents requires structural characterisation and understanding of their diverse mechanisms of action. As the cyclic hexapeptide cWFW (cyclo(RRRWFW)) does not exert its rapid cell killing activity by membrane permeabilisation, in this study we investigated alternative mechanisms of action, such as peptide translocation into the cytoplasm and peptide interaction with components of the phospholipid matrix of the bacterial membrane. Using fluorescence microscopy and an HPLC-based strategy to analyse peptide uptake into the cells we could confirm the cytoplasmic membrane as the major peptide target. However, unexpectedly we observed accumulation of cWFW at distinct sites of the membrane. Further characterisation of peptide-membrane interaction involved live cell imaging to visualise the distribution of the lipid cardiolipin (CL) and isothermal titration calorimetry to determine the binding affinity to model membranes with different bacterial lipid compositions. Our results demonstrate a distribution of the cyclic peptide similar to that of cardiolipin within the membrane and highly preferred affinity of cWFW for CL-rich phosphatidylethanolamine (POPE) matrices. These observations point to a novel mechanism of antimicrobial killing for the cyclic hexapeptide cWFW which is neither based on membrane permeabilisation nor translocation into the cytoplasm but rather on preferred partitioning into particular lipid domains. As the phospholipids POPE/CL play a key role in the dynamic organisation of bacterial membranes we discuss the consequences of this peptide-lipid-interaction and outline the impact on antimicrobial peptide research.
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.