Candida species are a major cause of invasive fungal infections. While Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are the most dominant species causing life-threatening candidiasis, C. auris recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic Candida infections with dissemination via the bloodstream and to elucidate the pathogenic potential of C. auris, we used an ex vivo whole blood infection model. Similar to other clinically relevant Candida spp., C. auris is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of C. auris-infected blood revealed a unique C. auris gene expression program during infection, while the host response proofed similar and conserved compared to other Candida species. C. auris-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 Candida species in our model, C. auris-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 C. auris cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into C. auris pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other Candida species.

Candida species are a major cause of invasive fungal infections. While Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are the most dominant species causing life-threatening candidiasis, C. auris recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic Candida infections with dissemination via the bloodstream and to elucidate the pathogenic potential of C. auris, we used an ex vivo whole blood infection model. Similar to other clinically relevant Candida spp., C. auris is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of C. auris-infected blood revealed a unique C. auris gene expression program during infection, while the host response proofed similar and conserved compared to other Candida species. C. auris-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 Candida species in our model, C. auris-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 C. auris cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into C. auris pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other Candida species.

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Table S8 — statistics for TCGA dataset. This table provides ANOVA and post hoc pairwise test statistics for the TCGA data application as described in section ‘Different cancer types possess notable differences in kynurenine and serotonin concentrations’. (XLS 11 kb)

S2 — example files. Zipped example files usable to review specific data file format or to check SBMLmod web application and service functionality. These files resemble the first use case with 32 tissues in the manuscript. Note that mapping files, the SBML model and the data file limited to 10 tissues, can also be downloaded from the web application ( http://sbmlmod.uit.no ) using the download link at the lower part of the webpage under ‘Example Files’. (ZIP 32 kb)

S7 — TCGA sample IDs. List of TCGA sample IDs used to calculate the results presented in Fig. 2 c and d. (TXT 76 kb)

Table S8 — statistics for TCGA dataset. This table provides ANOVA and post hoc pairwise test statistics for the TCGA data application as described in section ‘Different cancer types possess notable differences in kynurenine and serotonin concentrations’. (XLS 11 kb)

Table S6 — detailed statistical results for dataset of 32 tissues. This file provides ANOVA and post hoc pairwise test statistics for all 32 tissues that have been analysed and described in the subsection ’Tissue specific differences in tryptophan metabolites’. (XLS 71 kb)

Table S6 — detailed statistical results for dataset of 32 tissues. This file provides ANOVA and post hoc pairwise test statistics for all 32 tissues that have been analysed and described in the subsection ’Tissue specific differences in tryptophan metabolites’. (XLS 71 kb)

S7 — TCGA sample IDs. List of TCGA sample IDs used to calculate the results presented in Fig. 2 c and d. (TXT 76 kb)