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

Article Article scientifique Article Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa eng 2022-03 author Patrulea Viorica 813295 author Gan Bee-Ha author Perron Karl 45679 author Cai Xingguang author Abdel-Sayed Philippe author Sublet Emmanuelle 514013 author Ducret Verena 596806 author Porroche Nerhot Natalia 780720 author Applegate Lee Ann author Borchard Gerrit 0000-0001-6268-2586 635281 author Reymond Jean-Louis author Jordan Olivier 0000-0003-3752-2198 133859 119025 10.1016/j.carbpol.2021.119025 35027127 0144-8617 https://linkinghub.elsevier.com/retrieve/pii/S0144861721014120 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. Antimicrobial formulations Antimicrobial peptide dendrimers (AMPDs) Multidrug-resistant bacteria Synergistic antimicrobial activities Wound infections Dewey 615 Dewey 580 Unitec office of the University of Geneva 1037-A985 Swiss National Science Foundation (SNSF) P400PM_194482 31 Section des sciences pharmaceutiques 17 45 Département des sciences végétales 163 false 879 Biopharmacie Carbohydrate polymers 280 5c05a9a4-d108-43ae-8197-4cf3a804c7ea Article (Published version) Public 1-s2.0-S0144861721014120-main.pdf 10515142 application/pdf CC BY-NC-ND-4.0 openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté des sciences / Section de biologie / Département des sciences végétales

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Synergistic effects of antimicrobial peptide dendrimer-chitosan polymer conjugates against Pseudomonas aeruginosa	Carbohydrate polymers			2022	214	139

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