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J. Biol. Chem., Vol. 282, Issue 12, 8969-8977, March 23, 2007

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Fungal Peptide Destruxin A Plays a Specific Role in Suppressing the Innate Immune Response in Drosophila melanogaster^*

Subhamoy Pal, Raymond J. St. Leger, and Louisa P. Wu¹

From the Center for Biosystems Research, University of Maryland Biotechnology Institute and Department of Entomology, University of Maryland, College Park, Maryland 20742

Destruxins are a class of insecticidal, anti-viral, and phytotoxic cyclic depsipeptides that are also studied for their toxicity to cancer cells. They are produced by various fungi, and a direct relationship has been established between Destruxin production and the virulence of the entomopathogen Metarhizium anisopliae. Aside from opening calcium channels, their in vivo mode of action during pathogenesis remains largely uncharacterized. To better understand the effects of a Destruxin, we looked at changes in gene expression following injection of Destruxin A into the fruit fly Drosophila melanogaster. Microarray results revealed reduced expression of various antimicrobial peptides that play a major role in the humoral immune response of the fly. Flies co-injected with a non-lethal dose of Destruxin A and the normally innocuous Gram-negative bacteria Escherichia coli, showed increased mortality and an accompanying increase in bacterial titers. Mortality due to sepsis was rescued through ectopic activation of components in the IMD pathway, one of two signal transduction pathways that are responsible for antimicrobial peptide induction. These results demonstrate a novel role for Destruxin A in specific suppression of the humoral immune response in insects.

Received for publication, June 21, 2006 , and in revised form, December 21, 2006.

The amino acid sequence of this protein can be accessed through NCBI Protein Database under NCBI accession number GSE5767 [NCBI GEO] .

^* This work was supported by National Institutes of Health Grant R01-GM62316. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental data.

¹ To whom correspondence should be addressed: Center for Biosystems Research, University of Maryland Biotechnology Institute, 5115 Plant Sciences Bldg., College Park, MD 20742. Tel.: 301-405-5151; Fax: 301-314-9075; E-mail: wul{at}umbi.umd.edu.

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