From environmental adaptation to host survival: Attributes that mediate pathogenicity of <i>Candida auris</i>

<i>Candida</i> species are a major cause of invasive fungal infections. While <i>Candida albicans, C. glabrata, C. parapsilosis</i>, and <i>C. tropicalis</i> are the most dominant species causing life-threatening candidiasis, <i>C. auris</i> recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic <i>Candida</i> infections with dissemination <i>via</i> the bloodstream and to elucidate the pathogenic potential of <i>C. auris</i>, we used an <i>ex vivo</i> whole blood infection model. Similar to other clinically relevant <i>Candida</i> spp., <i>C. auris</i> is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of <i>C. auris</i>-infected blood revealed a unique <i>C. auris</i> gene expression program during infection, while the host response proofed similar and conserved compared to other <i>Candida</i> species. <i>C. auris</i>-specific responses included adaptation and survival strategies, such as counteracting oxidative burst of immune cells, but also expression of potential virulence factors, (drug) transporters, and cell surface-associated genes. Despite comparable pathogenicity to other <i>Candida</i> species in our model, <i>C. auris</i>-specific transcriptional adaptations as well as its increased stress resistance and long-term environmental survival, likely contribute to the high risk of contamination and distribution in a nosocomial setting. Moreover, infections of neutrophils with pre-starved <i>C. auris</i> cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into <i>C. auris</i> pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other <i>Candida</i> species.