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Drosomycin-Like Defensin, a Human Homologue of Drosophila melanogaster Drosomycin with Antifungal Activity

Departments of Medicine,¹ Nuclear Medicine,² Dermatology,³ Medical Microbiology, Radboud University Nijmegen Medical Center and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands,⁴ Divisions of Infectious Diseases,⁵ Biochemistry, University of Colorado Health Sciences Center, Denver, Colorado⁶

Received 1 February 2007/ Returned for modification 13 June 2007/ Accepted 23 November 2007

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.

Published ahead of print on 22 January 2008.