The Drosophila Baramicin polypeptide gene protects against fungal infection.

Mark Austin Hanson,Lianne B Cohen,Igor Iatsenko,Alice Marra,Bruno Lemaitre,Steven A Wasserman,Xiaorong Lin

doi:10.1371/journal.ppat.1009846

Abstract

The fruit fly Drosophila melanogaster combats microbial infection by producing a battery of effector peptides that are secreted into the haemolymph. Technical difficulties prevented the investigation of these short effector genes until the recent advent of the CRISPR/CAS era. As a consequence, many putative immune effectors remain to be formally described, and exactly how each of these effectors contribute to survival is not well characterized. Here we describe a novel Drosophila antifungal peptide gene that we name Baramicin A. We show that BaraA encodes a precursor protein cleaved into multiple peptides via furin cleavage sites. BaraA is strongly immune-induced in the fat body downstream of the Toll pathway, but also exhibits expression in other tissues. Importantly, we show that flies lacking BaraA are viable but susceptible to the entomopathogenic fungus Beauveria bassiana. Consistent with BaraA being directly antimicrobial, overexpression of BaraA promotes resistance to fungi and the IM10-like peptides produced by BaraA synergistically inhibit growth of fungi in vitro when combined with a membrane-disrupting antifungal. Surprisingly, BaraA mutant males but not females display an erect wing phenotype upon infection. Here, we characterize a new antifungal immune effector downstream of Toll signalling, and show it is a key contributor to the Drosophila antimicrobial response.

Highlights

The innate immune response provides the first line of defence against pathogenic infection
Using the fruit fly–a genetic workhorse of Biology–we recently showed that a class of host-encoded antibiotics called “antimicrobial peptides” are essential for defence against bacterial infection, but do not contribute as strongly to defence against fungi
We describe a novel antifungal peptide gene of fruit flies, and show that it is a major contributor to the fly antifungal defence response

Summary

Introduction

The innate immune response provides the first line of defence against pathogenic infection. In Drosophila, two NF-κB signalling pathways, the Toll and Imd pathways, regulate most inducible immune effectors: the Toll pathway is predominantly activated in response to infection by Gram-positive bacteria and fungi [5,6], while the immune-deficiency pathway (Imd) responds to the DAP-type peptidoglycan most commonly found in Gram-negative bacteria and a subset of Gram-positive bacteria [7]. Transcriptomic analyses have revealed that the systemic immune response encompasses far more than just the canonical AMPs. Many uncharacterized genes encoding small secreted peptides are induced to high levels downstream of the Toll and Imd pathways, pointing to the role for these peptides as immune effectors [11]. This is mainly due to the fact that these IMs belong to large gene families of small genes that were not typically disrupted using random mutagenesis [10,12]

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Discussion

Conclusion