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

## TL;DR

Researchers developed a fruit fly model to study how Candida auris, a dangerous fungus, interacts with the host's immune system, revealing new insights into infection mechanisms.

## Contribution

The study introduces a reliable Drosophila melanogaster model to investigate Candida auris-host interactions and identifies novel immune factors.

## Key findings

- Toll and JAK-STAT pathways mediate antifungal responses in Drosophila following C. auris infection.
- Conserved novel factors involved in host-C. auris interactions were identified.
- The Drosophila model enables high-throughput genetic screening for immune mechanisms and therapeutic strategies.

## Abstract

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.

This study demonstrates the potential of immunocompetent flies to establish a reliable and flexible infection model for investigating realistic interactions between the critical‐priority fungal pathogen Candida auris and the host. The susceptible infectious conditions can be optimized by selecting appropriate fly strains. The systemic and organ‐specific transcriptional profile facilitates the identification of novel factors implicated in C. auris‐induced pathogenesis, which may be overlooked in other models. This system enables high‐throughput genetic screening both for the molecular mechanisms underlying the host's response to C. auris and for the discovery of novel therapeutic strategies against this urgent fungal threat.