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

Louisa P Wu,Subhamoy Pal,Raymond J St Leger

doi:10.1074/jbc.m605927200

Louisa P Wu, Subhamoy Pal + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m605927200

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Abstract

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.

Highlights

Variety of insects can, at least in part, be attributed to secretion of virulence factors during pathogenesis
Destruxin Injection Causes a Reduction in Expression of Some Antimicrobial Peptide Genes—To test the effect of non-lethal doses of Destruxin on Drosophila gene expression, we compared wild-type flies injected with 86 ␮M Destruxin A to flies injected with phate-buffered saline (PBS) using cDNA microarrays
The dose was determined experimentally as the highest dose that could be injected into the fly without causing significant difference in mortality compared with PBS-injected flies within five days

Summary

Introduction

Variety of insects can, at least in part, be attributed to secretion of virulence factors during pathogenesis. 52% of microbial peptide genes, quantitative real time-PCR was used all antibacterial humoral response genes (GO:0006961) on the to examine Diptericin, Cecropin, Attacin, and Metchnikowin array were down-regulated in Destruxin-injected flies (Table expression (Fig. 2). If it is all noise, using a one- negative bacteria E. coli to determine whether Destruxins can standard-deviation criterion would result in ϳ15% of genes reduce AMP expression when the immune response has down-regulated in any given gene ontology category on nor- been activated.

Results

Conclusion