Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa.

Details

Serval ID
serval:BIB_40DB7D6879C5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa.
Journal
Carbohydrate polymers
Author(s)
Patrulea V., Gan B.H., Perron K., Cai X., Abdel-Sayed P., Sublet E., Ducret V., Nerhot N.P., Applegate L.A., Borchard G., Reymond J.L., Jordan O.
ISSN
1879-1344 (Electronic)
ISSN-L
0144-8617
Publication state
Published
Issued date
15/03/2022
Peer-reviewed
Oui
Volume
280
Pages
119025
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
We report herein a new chemical platform for coupling chitosan derivatives to antimicrobial peptide dendrimers (AMPDs) with different degrees of ramification and molecular weights via thiol-maleimide reactions. Previous studies showed that simple incorporation of AMPDs to polymeric hydrogels resulted in a loss of antibacterial activity and augmented cytotoxicity to mammalian cells. We have shown that coupling AMPDs to chitosan derivatives enabled the two compounds to act synergistically. We showed that the antimicrobial activity was preserved when incorporating AMPD conjugates into various biopolymer formulations, including nanoparticles, gels, and foams. Investigating their mechanism of action using electron and time-lapse microscopy, we showed that the AMPD-chitosan conjugates were internalized after damaging outer and inner Gram-negative bacterial membranes. We also showed the absence of AMPD conjugates toxicity to mammalian cells. This chemical technological platform could be used for the development of new membrane disruptive therapeutics to eradicate pathogens present in acute and chronic wounds.
Keywords
Animals, Anti-Bacterial Agents/chemistry, Anti-Bacterial Agents/pharmacology, Anti-Bacterial Agents/toxicity, Antimicrobial Peptides/chemistry, Antimicrobial Peptides/pharmacology, Antimicrobial Peptides/toxicity, Cell Membrane/drug effects, Cells, Cultured, Chitosan, Dendrimers, Drug Synergism, Hemolysis, Humans, Microbial Sensitivity Tests, Polymers, Pseudomonas aeruginosa/drug effects, Antimicrobial formulations, Antimicrobial peptide dendrimers (AMPDs), Multidrug-resistant bacteria, Synergistic antimicrobial activities, Wound infections
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2022 13:04
Last modification date
01/04/2022 6:34
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