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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Zoological research
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41017404/ |
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Table of Contents:
- Integrating a cationic backbone with a hydrophobic core: A structure-function strategy for designing self-assembling antimicrobial peptides with enhanced activity. Mwangi, James Tadese, Dawit Adisu Wang, Yi Asmamaw, Demeke Yang, Min Michira, Brenda B Khalid, Mehwish Wang, Zi-Yi Lu, Qiu-Min Lai, Ren Animals Mice Hydrophobic and Hydrophilic Interactions Anti-Bacterial Agents Structure-Activity Relationship Microbial Sensitivity Tests Klebsiella pneumoniae Antimicrobial Peptides Antimicrobial Cationic Peptides Methicillin-Resistant Staphylococcus aureus Biofilms Humans Effective countermeasures against multidrug-resistant nosocomial pathogens, such as carbapenem-resistant and methicillin-resistant (MRSA), require the development of innovative antimicrobial strategies. This study presents a structure-function approach to antimicrobial peptide (AMP) design through the strategic integration of a cationic backbone with a hydrophobic core. This dual-domain architecture enables robust hydrophobic and electrostatic interactions, promoting spontaneous self-assembly and efficient membrane engagement. The lead peptide, Tryptolycin (TRPY), formed stable, monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity, with minimum inhibitory concentrations ≤1 µmol/L against multiple strains of MRSA and , while exerting minimal cytotoxicity toward mammalian cells. TRPY achieved rapid bacterial elimination, eradicating 99.9% of both planktonic and persister populations within minutes. Mechanistic investigations revealed that TRPY induced membrane permeabilization, promoted reactive oxygen species (ROS) production, and inhibited biofilm formation. In murine infection models, TRPY effectively eradicated established infections, reducing bacterial burden across target organs by 3- to 5-fold without significant cytotoxicity at therapeutic concentrations. Collectively, these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.