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A Synthetic Cyclized Antimicrobial Peptide with Potent Effects against Drug-Resistant Skin Pathogens
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;Division of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Division of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.ORCID iD: 0000-0003-0919-5062
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Institute of Medical Sciences, University of Aberdeen, Ashgrove Road West, Foresterhill, Aberdeen AB25 2ZD, UK.ORCID iD: 0000-0002-6636-5809
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;Division of Clinical Microbiology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
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2023 (English)In: ACS - Infectious Diseases, E-ISSN 2373-8227, Vol. 9, no 5, p. 1056-1063Article in journal (Refereed) Published
Abstract [en]

Dermal infections requiring treatment are usually treated with conventional antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defense peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant-type strains and clinical isolates of common skin pathogens in the low (<2) μM range. In addition, it influences innate immunity in keratinocytes, and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes. Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic-resistant bacteria.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2023. Vol. 9, no 5, p. 1056-1063
Keywords [en]
keratinocytes, MRSA, synthetic antimicrobial peptide, LL-37, bactericidal peptide, wound closure
National Category
Nano Technology Dermatology and Venereal Diseases Pharmaceutical Sciences
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-509806DOI: 10.1021/acsinfecdis.2c00598ISI: 000984345000001PubMedID: 37132993OAI: oai:DiVA.org:uu-509806DiVA, id: diva2:1790496
Funder
Swedish Research Council, 2011-3403Olle Engkvists stiftelse, 186 678Region Stockholm, 995080Elisabeth och Alfred Ahlqvists stiftelseApotekarsocietetens Stipendiestiftelse för Vetenskaplig ForskningAvailable from: 2023-08-23 Created: 2023-08-23 Last updated: 2024-01-04Bibliographically approved

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Mohanty, SoumitraMuhammad, TajFerraz, NataliaGöransson, Ulf

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