Profiling the host defense responses against Candida auris in a reliable Drosophila melanogaster infection model.

The "superbug" Candida auris has been ranked as a priority fungal pathogen and is becoming a serious threat to public health. However, the underlying mechanisms of real-world pathogen-host interactions remain elusive, in part due to the lack of powerful immunocompetent animal models. Here, we report that selected wild-type strains of Drosophila melanogaster can be developed as a promising infection model to recapitulate C. auris systemic infection. The systemic and organ-specific responses to C. auris infection in vivo were evaluated, as well as the corresponding transcriptional profiling. Our findings confirmed that Toll and JAK-STAT signaling pathways mediate antifungal responses in the Drosophila model following C. auris infection. Moreover, we identified certain conserved novel factors required for host-C. auris interactions, highlighting the fly model's potential to reveal subtle immune mechanisms not readily observed in mammalian systems. Taken together, our work demonstrates that wild-type Drosophila offers a robust immunocompetent animal model for further in-depth investigation of dynamic C. auris-host interactions in vivo.