Profiling the host defense responses against <i>Candida auris</i> in a reliable <i>Drosophila melanogaster</i> infection model

The "superbug" <i>Candida auris</i> 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 <i>Drosophila melanogaster</i> can be developed as a promising infection model to recapitulate <i>C. auris</i> systemic infection. The systemic and organ-specific responses to <i>C. auris</i> infection <i>in vivo</i> were evaluated, as well as the corresponding transcriptional profiling. Our findings confirmed that Toll and JAK-STAT signaling pathways mediate antifungal responses in the <i>Drosophila</i> model following <i>C. auris</i> infection. Moreover, we identified certain conserved novel factors required for host-<i>C. auris</i> 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 <i>Drosophila</i> offers a robust immunocompetent animal model for further in-depth investigation of dynamic <i>C. auris</i>-host interactions <i>in vivo</i>.