Unravelling the role of Candida albicans Prn1 in the Oxidative stress response through a proteomic approach. Study of Prn1 orthologues

Candida albicans Prn1 is a protein that shares similarities with mammalian Pirin but with an unknown function in the yeast. Orthologues of Prn1 have been identified in other pathogenic fungi but not in Saccharomyces cerevisiae, suggesting a relationship with pathogenesis. Prn1 increase in abundance after H₂O₂ treatment has been previously shown [1]. Quantitative proteomic assay (DDA-MS) in a wild-type (SN250) and a prn1∆ strains treated with hydrogen peroxide identified around 1,800 proteins. These assays indicated a lower increase of proteins with oxidoreductase activity after treatment in the prn1∆ strain compared to the wild-type, as well as an increase in proteasome-activating proteins and a decrease in translation-involved proteins. Accordingly, Prn1 absence, under H₂O₂ treatment, led to a lower survival rate and a higher percentage of apoptosis, together with higher reactive oxygen species levels and higher proteasome activity. Besides, remarkable differences in the abundance of some transcription factors were observed between prn1∆ mutant and wild-type strains. Among them, Mnl1, involved in Prn1 expression, Nrg1, a Mnl1 antagonist, or Bas1, presented an inverse pattern of expression between both strains. Interestingly, orf19.4850, a protein orthologue to S. cerevisiae Cub1, was only expressed in the wild-type strain under the oxidative stress. Studies with the orf19.4850∆/orf19.4850 mutant strain have shown its involvement in the response to H₂O₂ and in proteasome function. Under basal conditions, the proteomics results also suggest a possible involvement of Prn1 in mitochondrial oxidative stress detoxication. All the experiments confirm Prn1 as a relevant actor in C. albicans oxidative response.

Surprisingly, the Prn1 orthologues, Prn2, Prn3 and Prn4, have not shown a redundant function or expression. The proteomics analyses only detected a slight but significant increase in Prn4 abundance, which is the most similar to Prn1, in the wild-type strain after H₂O₂ treatment, but not in the prn1∆. Prn2 and Prn3 were not detected in any of the four conditions studied. Thus, we are currently studying the role of Prn2, Prn3 and Prn4 under oxidative stress and other conditions that could give us a clue about their function.

Amador-García A, et al. mSystems. 2021