Deciphering the antigenic profile and the response to oxidative stress of the pathogenic fungus Candida auris

Abstract

The difficulty of accurately identifying the fungus Candida auris and the high resistance rates presented has increased the concern on the healthcare setting. Due to this, the objectives of this thesis were to determine the C. auris-specific antigens by using sera from infected mice and to analyse the fungal response to oxidative stress. The results obtained indicated that the non-aggregative isolate exhibited greater virulence than the aggregative one. Furthermore, Eno, Pgk, Gapdh and Pgm were identified as C. auris-specific antigens, which were recognised by both mice and human sera obtained from individuals with disseminated infections caused by C. auris, but not by sera obtained from mice infected with other fungal species. On the other hand, overexpression of peroxiredoxin Tsa1b under oxidative stress was identified by both genic and proteomic approaches and its antigenicity was also confirmed. The characterisation of the C. auris ¿TSA1B strain demonstrated a greater susceptibility to stresses and to the presence of dendritic cells and bone marrow-derived macrophages than the WT strain. Furthermore, the in vivo infections performed on Galleria mellonella and mice showed the involvement of Tsa1b in the development of disseminated infection. In conclusion, this thesis has allowed a more comprehensive understanding of the pathobiology of C. auris by the determination of specific antigenic markers and by analysing the role of the Tsa1b peroxiredoxin in the infective process carried out by the fungus.