1. Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns
- Author
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Christian van Delden, Wassim Raffoul, Lee Ann Applegate, Yok-Ai Que, Thissa N. Siriwardena, Alexandre Luscher, Laurence G. Rahme, Thilo Köhler, Murielle Michetti, Jean-Louis Reymond, and Paris Jafari
- Subjects
Pore Forming Cytotoxic Proteins ,Dendrimers ,Multidrug tolerance ,Cell- and Tissue-Based Therapy ,Pharmaceutical Science ,Virulence ,MvfR ,Organic chemistry ,610 Medicine & health ,medicine.disease_cause ,Article ,Analytical Chemistry ,Microbiology ,Cell therapy ,03 medical and health sciences ,PqsR ,QD241-441 ,Drug Discovery ,540 Chemistry ,medicine ,Humans ,Pseudomonas Infections ,Physical and Theoretical Chemistry ,Progenitor cell ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,burn wound ,030306 microbiology ,Chemistry ,antimicrobial peptide dendrimers ,quorum-sensing inhibitors ,Quorum Sensing ,anti-infection dressing ,biological bandage ,Pathogenic bacteria ,Antimicrobial ,Anti-Bacterial Agents ,Multiple drug resistance ,Quorum sensing ,Chemistry (miscellaneous) ,Pseudomonas aeruginosa ,Molecular Medicine ,570 Life sciences ,biology ,cell therapy ,Burns - Abstract
Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells.
- Published
- 2021