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  • 1.
    Björn, Camilla
    et al.
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Mahlapuu, M.
    Mattsby-Baltzer, I.
    Håkansson, Joakim
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r2016In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 81, p. 21-28Article in journal (Refereed)
    Abstract [en]

    Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50 μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections.

  • 2. Stensen, Wenche
    et al.
    Turner, Rob
    Brown, Marc
    Kondori, Nahid
    Svendsen, John Sigurd
    Svenson, Johan
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Short cationic antimicrobial peptides display superior antifungal activities toward Candidiasis and Onychomycosis in comparison with Terbinafine and Amorolfine2016In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392Article in journal (Refereed)
    Abstract [en]

    Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.

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