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

Patrulea, Viorica; Gan, Bee-Ha; Perron, Karl; Cai, Xingguang; Abdel-Sayed, Philippe; Sublet, Emmanuelle; Ducret, Verena; Nerhot, Natalia Porroche; Applegate, Lee Ann; Borchard, Gerrit; Reymond, Jean-Louis; Jordan, Olivier (15 March 2022). Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa. Carbohydrate polymers, 280, p. 119025. Elsevier 10.1016/j.carbpol.2021.119025

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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.

Item Type:

Newspaper or Magazine Article

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Gan, Bee Ha, Cai, Xingguang, Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0144-8617

Publisher:

Elsevier

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

26 Jan 2023 15:19

Last Modified:

05 Feb 2023 02:25

Publisher DOI:

10.1016/j.carbpol.2021.119025

PubMed ID:

35027127

BORIS DOI:

10.48350/177597

URI:

https://boris.unibe.ch/id/eprint/177597

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