The oxidative stress-related peroxiredoxin Tsa1b of Candidozyma (Candida) auris contributes to virulence and infection

The difficulty of accurately identifying Candidozyma auris (formerly Candida auris) and the high resistance rates presented have increased the concern in the healthcare setting. Due to this, the aim of this study was to analyse the fungal response to oxidative stress. To achieve this goal, gene and protein expression were examined using qPCR and two-dimensional electrophoresis, respectively, peroxiredoxin Tsa1b being found to be upregulated under oxidative stress. Subsequently, the significance of Tsa1b was next investigated by characterizing the C. auris Δtsa1b and C. auris Δtsa1b::TSA1B strains generated by CRISPR-Cas9. The findings demonstrated that the Δtsa1b strain was more susceptible to oxidative and cell wall stressors than the wild-type strain, which was consistent with an increase in the cell wall β-glucan amounts when grown in the presence of oxidative stress. Importantly, Tsa1b has also been detected as an antigen by patient sera. Furthermore, the Δtsa1b strain was also more vulnerable to the presence of dendritic cells and bone marrow-derived macrophages. Finally, in vivo infections performed in Galleria mellonella and mice showed a slower progression of the disease in animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as a potential candidate to be studied as a virulence factor implicated in the oxidative stress response of C. auris. These findings advance the knowledge of the pathobiology of C. auris and point out the potential of Tsa1b for the development of new diagnostic and therapeutic approaches.