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 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 42 o C. Transcriptomic analysis of the 20-1498 strain suggests that in addition to glucose and iron homeostasis, autophagy and cell membrane fluidity play roles in thermal stress conditions. In silico analysis showed the interaction of pepstatin A with the catalytic domain of Yps1 and Yps7. This inhibitor, together with caffeine, had a subtle effect on the growth of C. auris. However, these compounds induce alterations in 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 target of new antifungal or antivirulence agents. RNA-seq profile of Candidozyma auris clade IV strain 20-1498 from stationary-phase YPD cultures at 37°C, subsequently incubated at 37°C and 42°C for six hours in YNB medium with 2% dextrose and 0.5% (NH4)2SO4.