Phenotypic Impact and Multivariable Assessment of Antifungal Susceptibility in Candida auris Survival Using a Galleria mellonella Model

The novel pathogen <i>Candida auris</i> has rapidly become a major health threat due to its high virulence, resistance to multiple antifungal agents, and remarkable environmental persistence. This study evaluated the influence of phenotypic traits and antifungal minimum inhibitory concentrations (MICs) on <i>C. auris</i> virulence using a <i>Galleria mellonella</i> infection model. Ten clinical strains, categorized as aggregative or non-aggregative, were analyzed for antifungal susceptibility and survival outcomes. All strains exhibited fluconazole resistance, with variable susceptibilities to other antifungals. Survival analysis revealed that the non-aggregative phenotype was independently associated with reduced survival in <i>G. mellonella</i> (HR = 2.418, <i>p</i> = 0.015), while antifungal MICs and invasive origin were not significant independent predictors of mortality in an elastic net-adjusted multivariable model. Strong correlations were observed between certain antifungal MICs, suggesting potential cross-resistance patterns; however, no independent association with virulence was identified. These results suggest that <i>C. auris</i> possesses not only an enhanced ability to develop antifungal resistance but also the capacity to do so without incurring fitness costs that could attenuate its virulence.