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The BaramicinA gene is required at several steps of the host defense against Enterococcus faecalis and Metarhizium robertsii in a septic wound infection model in Drosophila melanogaster

By Jianqiong Hunag, Yanyan Lou, Jiyong Liu, Philippe Bulet, Renjie Jiao, Jules A Hoffmann, Samuel Liegeois, Zi Li, Dominique Ferrandon

Posted 23 Nov 2020
bioRxiv DOI: 10.1101/2020.11.23.394809

The host defense against several Gram-positive bacterial and fungal infections is mostly mediated by the Toll pathway in Drosophila, which regulates the expression of multiple genes including effectors of the innate immune response. One such potential effector is IMPPP/BaraA, a precursor protein that is processed at furin cleavage sites into an armamentarium of small DIM peptides that display a high degree of sequence similarity. We report here the generation of multiple mutants affecting this gene. Our phenotypic analysis revealed a specific sensitivity to pathogens belonging to distinct kingdoms, the Gram-positive bacterium Enterococcus faecalis and the entomopathogenic fungus Metarhizium anisopliae, only in septic injury models of infection. Unexpectedly, we failed to reveal a consistently increased microbial burden in the mutant flies infected with either of these microorganisms, opening the possibility for a role of BaraA in resilience rather than in resistance, which we were however unable to confirm. We also found that some BaraA-derived DIM peptides display an antimicrobial activity at millimolar concentrations in vitro. BaraA is additionally required for an efficient cleavage of pro-phenol oxidase into an active enzyme. BaraA is also involved in the cellular host defense, but through distinct mechanisms: it needs to be expressed in hemocytes for an efficient response solely to E. faecalis infection whereas it is required for the uptake by plasmatocytes of M. robertsii conidia. We propose a model whereby BaraA secreted by hemocytes may act at a very short range and protect host tissues or organs targeted specifically by E. faecalis. This study thus reveals an unexpected functional complexity of a potential effector of the Toll pathway in the host defense against specific infections.

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