CauYAP1 encodes a transcription factor that regulates the environmental stress tolerance of Candidozyma auris

Background Components and regulation of the oxidative stress defense system of Candidozyma auris are important for fungal survival in hostile ecological and anatomical niches. Methods We investigated the functional role of the oxidative stress response regulator CauYap1 bZIP-type transcription factor by generating and physiologically characterizing ΔCauYAP1 deletion mutant strains. Results Loss of CauYAP1 significantly increased sensitivity to oxidative stressors, including H 2 O 2 , tert -butyl hydroperoxide ( t BOOH), diamide, and NaOCl, to heat stress, CdCl 2 exposures on YPD2 agar, and reduced growth under iron-limiting conditions in YNB static liquid cultures supplemented with deferiprone. t BOOH-triggered up-regulation of TRR1 thioredoxin reductase and TSA1 peroxiredoxin genes was under CauYap1 control. Unexpectedly, deletion of CauYAP1 resulted in a slight increase in MIC values for AMB. In a mouse model of disseminated infection, the 10Δ gene-deletion mutant exhibited a statistically non-significant trend toward reduced virulence, characterized by delayed mortality. Nevertheless, under AMB treatment, a strong trend toward higher C. auris clearance (p=0.0608) was observed in the kidneys of 10Δ -infected mice compared to those infected with the wild-type strain. Immunostimulation studies demonstrated a strong cytokine response to C. auris cells in human monocyte-derived dendritic cells and macrophages, but deletion of CauYAP1 did not result in any changes in cytokine/chemokine responses or any differences in phagocytic killing. Finally, both 10Δ mutant and wild-type strains colonized human skin explants with similar efficiency without penetrating the stratum corneum. Conclusion The CauYap1 bZIP-type transcription factor plays a role in tolerance to environmental stress and may contribute to the virulence of C. auris .