Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Small (Weinheim an der Bergstrasse, Germany)
2025
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40965309/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Table of Contents:
- A Self-Assembling Peptide with Nanoparticle-to-Fibril Transformation Exhibits Multimodal Antimicrobial Activity through Membrane Disruption and Quorum-Sensing Inhibition. Mwangi, James Asmamaw, Demeke Yang, Min Tadese, Dawit Adisu Michira, Brenda B Wang, Yi Zhou, Sheng-Wen Wang, Gan Wang, Ziyi Lu, Qiu-Min Lai, Ren Quorum Sensing Nanoparticles Biofilms Pseudomonas aeruginosa Peptides Staphylococcus aureus Animals Cell Membrane Anti-Bacterial Agents Mice Microbial Sensitivity Tests Anti-Infective Agents Quorum sensing (QS) plays a crucial role in biofilm formation, virulence, and antibiotic resistance, making it an attractive target for combating multidrug-resistant pathogens. Here, self-assembling peptides are designed by incorporating amphiphilic monomers with distinct hydrophobic and hydrophilic termini to achieve optimal self-assembly dynamics and interaction with bacterial membranes. The lead peptide, SAP2-PEG, spontaneously forms nanoparticles that transform into fibrillar networks under membrane-mimicking conditions. The peptide exhibits potent antimicrobial activity against critical nosocomial pathogens at low micromolar concentrations and disrupts both pre-formed and nascent polymicrobial biofilms. Mechanistically, SAP2-PEG disrupts bacterial membranes while simultaneously inhibiting QS by downregulating key genes, including the las and rh1 systems in Pseudomonas aeruginosa, and the agr system components in Staphylococcus aureus, as validated through transcriptome analysis. Notably, the peptide showed effectiveness against polymicrobial biofilms in both wound and catheter-associated infections. In vivo, it significantly reduced P. aeruginosa lung and S. aureus systemic infection. These findings establish SAP2-PEG as a promising therapeutic candidate that combines direct antimicrobial action with QS disruption for combating biofilm-associated infections.