The oxidative stress response-related peroxiredoxin Tsa1b of Candida auris functions as a virulence factor that promotes infection

Abstract

The difficulty of accurately identifying 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 discovered to be overexpressed under oxidative stress. Besides, its antigenicity was also confirmed by western blotting. Subsequently, the significance of Tsa1b was next investigated by creating and characterizing the C. auris {Delta}TSA1B and C. auris {Delta}TSA1B::TSA1B strains using CRISPR-Cas9. The findings demonstrated that the{Delta} TSA1B 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 {beta}-glucan amounts when grown in the presence of oxidative stress. Furthermore, the{Delta} TSA1B 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 those animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as an important protein for the C. auris response to oxidative stress and as a virulence factor, allowing for a more thorough knowledge of the pathobiology of this yeast. This study points out the potential that this protein may have for the development of new diagnostic and therapeutic approaches. HIGHLIGHTSO_LISeveral metabolic proteins are implicated in C. auris response to oxidative stress C_LIO_LIC. auris response to oxidative stress is influenced by the Tsa1b peroxiredoxin C_LIO_LILack of Tsa1b generates more susceptibility to stresses and an altered cell wall C_LIO_LIC. auris Tsa1b is involved in the fungal interaction with host immune cells C_LIO_LIThe Tsa1b of C. auris contributes to the progression of the infection in vivo C_LI