Drosomycin-like defensin, a human homologue of Drosophila melanogaster drosomycin with antifungal activity.
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.
Simon
Anna
A
Department of Medicine 463, Radboud University Nijmegen Medical Center, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands.
Kullberg
Bart Jan
BJ
Tripet
Brian
B
Boerman
Otto C
OC
Zeeuwen
Patrick
P
van der Ven-Jongekrijg
Johanna
J
Verweij
Paul
P
Schalkwijk
Joost
J
Hodges
Robert
R
van der Meer
Jos W M
JW
Netea
Mihai G
MG
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
D000935:Antifungal Agents; D023082:Defensins; D029721:Drosophila Proteins; C091227:DRS protein, Drosophila