title: Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r.
abstract: 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 3-50μg/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 400μg/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.
authors.affiliation: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; SP Technical Research Institute of Sweden, Medical Device Technology, Box 857, SE-501 15 Borås, Sweden; The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Blå stråket 5, SE-413 45 Gothenburg, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Björn
authors.affiliation: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Blå stråket 5, SE-413 45 Gothenburg, Sweden.
authors.forename: Margit
authors.initials: M
authors.lastname: Mahlapuu
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Box 440, SE-405 30 Gothenburg, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Mattsby-Baltzer
authors.affiliation: Pergamum AB, Karolinska Institutet Science Park, Fogdevreten 2, SE-171 65 Solna, Sweden; SP Technical Research Institute of Sweden, Medical Device Technology, Box 857, SE-501 15 Borås, Sweden. Electronic address: joakim.hakansson@sp.se.
authors.forename: Joakim
authors.initials: J
authors.lastname: Håkansson
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002179:Candidiasis, Cutaneous / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D018709:Statistics, Nonparametric; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014946:Wound Infection / Q000188:drug therapy / Q000382:microbiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D023181:Antimicrobial Cationic Peptides; D007781:Lactoferrin; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C051321:SERPINE1 protein, human
keywords: AMP; Antibiotic resistance; Candida albicans; MRSA; Staphylococcus aureus; Wound infection