Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns

Paris Jafari; Alexandre Luscher; Thissa Siriwardena; Murielle Michetti; Yok-Ai Que; Laurence G Rahme; Jean-Louis Reymond; Wassim Raffoul; Christian Van Delden; Lee Ann Applegate; Thilo Köhler

doi:10.3390/molecules26133839

Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns

Molecules. 2021 Jun 24;26(13):3839. doi: 10.3390/molecules26133839.

Authors

Paris Jafari^{1

2

3}, Alexandre Luscher⁴, Thissa Siriwardena⁵, Murielle Michetti^{1

2}, Yok-Ai Que⁶, Laurence G Rahme^{7

8

9}, Jean-Louis Reymond⁵, Wassim Raffoul², Christian Van Delden^{4

10}, Lee Ann Applegate^{1

2

11

12}, Thilo Köhler^{4

10}

Affiliations

¹ Regenerative Therapy Unit (UTR), Department of Musculoskeletal Medicine DAL, Lausanne University Hospital, 1011 Lausanne, Switzerland.
² Service of Plastic, Reconstructive & Hand Surgery, Lausanne University Hospital, 1011 Lausanne, Switzerland.
³ Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
⁴ Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁵ Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland.
⁶ Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
⁷ Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.
⁸ Shriners Hospitals for Children Boston, Boston, MA 02114, USA.
⁹ Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Division on Infectious Disease and Transplantation, University Hospital of Geneva, 1205 Geneva, Switzerland.
¹¹ Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
¹² Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215028, China.

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.

Keywords: MvfR; PqsR; anti-infection dressing; antimicrobial peptide dendrimers; biological bandage; burn wound; cell therapy; quorum-sensing inhibitors.

MeSH terms

Anti-Bacterial Agents* / chemistry
Anti-Bacterial Agents* / pharmacology
Burns* / microbiology
Burns* / pathology
Burns* / therapy
Cell- and Tissue-Based Therapy*
Cells, Cultured
Dendrimers* / chemistry
Dendrimers* / pharmacology
Humans
Pore Forming Cytotoxic Proteins* / chemistry
Pore Forming Cytotoxic Proteins* / pharmacology
Pseudomonas Infections / drug therapy*
Pseudomonas Infections / metabolism
Pseudomonas Infections / mortality
Pseudomonas aeruginosa / growth & development*
Quorum Sensing / drug effects*

Substances

Anti-Bacterial Agents
Dendrimers
Pore Forming Cytotoxic Proteins

Grants and funding

200020_159941/SNSF_/Swiss National Science Foundation/Switzerland