Profiling the host defense responses against the emerging fungal pathogen Candida auris in a reliable Drospophila 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. In this study, we report that selected wild-type strains of Drosophila melanogaster can be developed as a promising infection model to recapitulate C. auris bloodstream infection. The systemic and organ-specific responses to C. auris infection in vivo were evaluated, as well as the corresponding transcriptional profiling. Our findings confirm 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 the further in-depth investigation of dynamic C. auris-host interactions in vivo. Overall design: To investigate the effects of Candida auris infection on the host transcriptome in Drosophila melanogaster, we performed a series of experiments involving infection and control groups. Adult flies were injected with either C. auris or PBS as a control. We collected samples at two time points post-infection: 6 hours and 24 hours. At each time point, we either harvested whole flies or dissected the fat body tissue for analysis.