In vitro and in vivo antibacterial properties of peptide AMC-109 impregnated wound dressings and gels

• Published in: Journal of antibiotics Vol. 74; no. 5; pp. 337 - 345
• Main Authors: Håkansson, Joakim, Cavanagh, Jorunn Pauline, Stensen, Wenche, Mortensen, Bjarte, Svendsen, John-Sigurd, Svenson, Johan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2021; Nature Publishing Group
• Subjects: 14/19; 631/154/309/2144; 64/60; 692/308/1426; Animals; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; antibiotics; Bacteriology; Bandages; Biomedical and Life Sciences; Bioorganic Chemistry; Biotechnology & Applied Microbiology; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; cationic antimicrobial peptides; Diterpenes - pharmacology; Drug Design; efficacy; Farmakologi och toxikologi; Female; Fusidic Acid - pharmacology; Gels; Immunology; Infections; Life Sciences; Medicinal Chemistry; methicillin-resistant; Mice; Mice, Inbred BALB C; Microbiology; mouse model; Organic Chemistry; Peptides; peptidomimetics; Pharmacology & Pharmacy; Pharmacology and Toxicology; Pilot Projects; Pore Forming Cytotoxic Proteins - chemistry; Pore Forming Cytotoxic Proteins - pharmacology; Skin; stability; Staphylococcus aureus - drug effects; staphylococcus-aureus; Wound Healing
• ISSN: 0021-8820; 1881-1469; 1881-1469
• DOI: 10.1038/s41429-021-00406-5

Synthetic mimics of antimicrobial peptides (AMPs) is a promising class of molecules for a variety of antimicrobial applications. Several hurdles must be passed before effective systemic infection therapies with AMPs can be achieved, but the path to effective topical treatment of skin, nail, and soft tissue infections appears less challenging to navigate. Skin and soft tissue infection is closely coupled to the emergence of antibiotic resistance and represents a major burden to the healthcare system. The present study evaluates the promising synthetic cationic AMP mimic, AMC-109, for treatment of skin infections in vivo. The compound is evaluated both in impregnated cotton wound dressings and in a gel formulation against skin infections caused by
Staphylococcus aureus
and methicillin resistant
S. aureus
. Both the ability to prevent colonization and formation of an infection, as well as eradicate an ongoing infection in vivo with a high bacterial load, were evaluated. The present work demonstrates that AMC-109 displays a significantly higher antibacterial activity with up to a seven-log reduction in bacterial loads compared to current clinical standard therapy; Altargo cream (1% retapamulin) and Fucidin cream (2% fusidic acid) in the in vivo wound models. It is thus concluded that AMC-109 represents a promising entry in the development of new and effective remedies for various skin infections.