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Structure-Activity Relationship Study to Develop Peptide Amphiphiles as Species-Specific Antimicrobials.

Authors :
Pereira AJ
Xing H
de Campos LJ
Seleem MA
de Oliveira KMP
Obaro SK
Conda-Sheridan M
Source :
Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Mar 12; Vol. 30 (15), pp. e202303986. Date of Electronic Publication: 2024 Jan 24.
Publication Year :
2024

Abstract

Antimicrobial peptide amphiphiles (PAs) are a promising class of molecules that can disrupt the bacterial membrane or act as drug nanocarriers. In this study, we prepared 33 PAs to establish supramolecular structure-activity relationships. We studied the morphology and activity of the nanostructures against different Gram-positive and Gram-negative bacterial strains (such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii). Next, we used principal component analysis (PCA) to determine the key contributors to activity. We found that for S. aureus, the zeta potential was the major contributor to the activity while Gram-negative bacteria were more influenced by the partition coefficient (LogP) with the following order P. aeruginosa>E. coli>A. baumannii. We also performed a study of the mechanism of action of selected PAs on the bacterial membrane assessing the membrane permeability and depolarization, changes in zeta potential and overall integrity. We studied the toxicity of the nanostructures against mammalian cells. Finally, we performed an in vivo study using the wax moth larvae to determine the therapeutic efficacy of the active PAs. This study shows cationic PA nanostructures can be an intriguing platform for the development of nanoantibacterials.<br /> (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Details

Language :
English
ISSN :
1521-3765
Volume :
30
Issue :
15
Database :
MEDLINE
Journal :
Chemistry (Weinheim an der Bergstrasse, Germany)
Publication Type :
Academic Journal
Accession number :
38221408
Full Text :
https://doi.org/10.1002/chem.202303986