Abstract
The fruit fly Drososphila melanogaster combats microbial infection by producing a battery of effector peptides that are secreted into the haemolymph. The existence of many effectors that redundantly contribute to host defense has hampered their functional characterization. As a consequence, the logic underlying the role of immune effectors is only poorly defined, and exactly how each gene contributes 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 the nervous system. Importantly, we show that flies lacking BaraA are viable but susceptible to a subset of filamentous fungi. 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 males but not females display an erect wing phenotype upon infection, pointing a protective role of BaraA on the wing muscle or the nervous system. Collectively, we identify a new antifungal immune effector downstream of Toll signalling, improving our knowledge of the Drosophila antimicrobial response.
Significance statement Antimicrobial peptides (AMPs) of the innate immune system provide a front line of defence against infection. Recently AMPs have been implicated in physiological processes including inflammation, aging, and neurodegeneration. Drosophila melanogaster has been a useful model for understanding AMP functions and specificities in vivo. Here we describe a new Drosophila AMP family, Baramicin, which protects flies against fungal infection. The Baramicin polypeptide structure is also unique amongst animal AMPs, encoding multiple peptides on a single protein precursor cleaved by furin. Furthermore Baramicin mutants display a behavioural response to infection, suggesting Baramicin AMPs interact with more than just pathogens. Baramicin adds to our knowledge of the potent Drosophila antifungal response, and to growing observations of AMPs acting in seemingly non-canonical roles.
Competing Interest Statement
The authors have declared no competing interest.