The GPI-Anchored Aspartyl Proteases Encoded by the YPS1 and YPS7 Genes of Candidozyma Auris and Their Role Under Stress Conditions

Candidozyma auris is a multidrug resistance opportunistic pathogen, distinguished from Candida yeasts because of their thermotolerance, osmotolerance, and persistence in biotic and abiotic surfaces, attributes that seem linked to the cell wall composition. Here, seven putative genes encoding yapsins, extracellular aspartyl proteases GPI-anchored to the membrane or cell wall, were identified in the genomes of C. auris strains CJ97 and 20-1498, from clades III and IV, respectively. C. auris YPS1 gene is orthologous to the SAP9 of C. albicans. The YPS7 gene is orthologous to YPS7 of C. glabrata and S. cerevisiae, so they could coincide in roles. The CauYPS1 and CauYPS7 expression increased under nutrient starvation, 1.5 M NaCl, and at 42oC. In silico analysis suggests the interaction of pepstatin A, an aspartyl protease inhibitor, with the catalytic domain of Yps1 and Yps7. This inhibitor, in concert with caffeine, had a subtle effect on the growth of C. auris strains. However, these compounds induce alterations in the appearance of the cell wall. Thereby, yapsins CauYps1 and CauYps7 may play a role in the cell wall integrity of C. auris in stress conditions, and they could be a therapeutic target for the design of new antifungal or antivirulence agents.