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PMID:18212107

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Citation

Simon, A, Kullberg, BJ, Tripet, B, Boerman, OC, Zeeuwen, P, van der Ven-Jongekrijg, J, Verweij, P, Schalkwijk, J, Hodges, R, van der Meer, JW and Netea, MG (2008) Drosomycin-like defensin, a human homologue of Drosophila melanogaster drosomycin with antifungal activity. Antimicrob. Agents Chemother. 52:1407-12

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.

Links

PubMed PMC2292511 Online version:10.1128/AAC.00155-07

Keywords

Amino Acid Sequence; Animals; Antifungal Agents/chemical synthesis; Antifungal Agents/chemistry; Antifungal Agents/pharmacology; Aspergillus/classification; Aspergillus/drug effects; Defensins/chemical synthesis; Defensins/chemistry; Defensins/metabolism; Defensins/pharmacology; Drosophila Proteins/chemistry; Drosophila Proteins/pharmacology; Drosophila melanogaster/metabolism; Fungi/classification; Fungi/drug effects; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Homology, Amino Acid; Skin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FAM3A

involved_in

GO:0019732: antifungal humoral response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAM3A

involved_in

GO:0061844: antimicrobial humoral immune response mediated by antimicrobial peptide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAM3A

involved_in

GO:1905035: negative regulation of antifungal innate immune response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DMYC

involved_in

GO:0019732: antifungal humoral response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DMYC

involved_in

GO:0061844: antimicrobial humoral immune response mediated by antimicrobial peptide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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