title: Drosomycin-like defensin, a human homologue of Drosophila melanogaster drosomycin with antifungal activity.
abstract: Innate antifungal defense in Drosophila melanogaster relies on the activation of the Toll molecule and the release of drosomycin, a defensin-like molecule with antifungal properties. Ten human homologues of Toll have been described, with central roles in activation of the innate host defense. In the present study, we report a putative human homologue of the Drosophila-derived drosomycin, designated drosomycin-like defensin (DLD). Synthetic DLD displays a broad spectrum of activity against Aspergillus spp. and other clinically relevant filamentous fungi. These effects are specific for filamentous fungi; no activity has been found against yeasts or gram-positive or gram-negative bacteria. Synthetic DLD also displays immunomodulatory effects on Aspergillus-stimulated cytokine production. In addition, we show the expression of DLD mRNA in several human tissues, particularly in the skin, consistent with its putative role as a defensin against invading microorganisms. This is the first indication of an endogenous human peptide with specific antifungal activity, which is probably central in the defense against infections with molds.
authors.affiliation: Department of Medicine 463, Radboud University Nijmegen Medical Center, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Simon
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Brian
authors.initials: B
authors.lastname: Tripet
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Patrick
authors.initials: P
authors.lastname: Zeeuwen
authors.forename: Johanna
authors.initials: J
authors.lastname: van der Ven-Jongekrijg
authors.forename: Paul
authors.initials: P
authors.lastname: Verweij
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Robert
authors.initials: R
authors.lastname: Hodges
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001230:Aspergillus / Q000145:classification / Q000187:drug effects; D023082:Defensins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D029721:Drosophila Proteins / Q000737:chemistry* / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000378:metabolism; D005658:Fungi / Q000145:classification / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D023082:Defensins; D029721:Drosophila Proteins; C091227:DRS protein, Drosophila