The Drosophila Baramicin polypeptide gene protects against fungal infection

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.
Author summary The ways that animals combat infection involve complex molecular pathways that are triggered upon microbial challenge. While a great deal is known about which pathways are key to a successful defence response, far less is known about exactly what elements of that response are critical to combat a given 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. However a number of fly immune peptides remain uncharacterized, possibly explaining this gap in our understanding of the fly antifungal defence. Here we describe a novel antifungal peptide gene of fruit flies, and show that it is a major contributor to the fly antifungal defence response. We also found that this gene seems to regulate a behaviour that flies perform after infection, paralleling exciting recent findings that these genes are involved in neurological processes. Collectively, we clarify a key part of the fly antifungal defence, and contribute an important piece to help explain the logical organization of the immune defence against microbial infection.