(A) The conserved domain structure of the C. neoformans Ire1 protein. (B) For sensitive test to UPR- and cell wall- stresses, wild-type (H99), ire1 (YSB552 and YSB554), and ire1+IRE1 (YSB1000 and YSB1005) strains were serially diluted and spotted on YPD media with or without exposure to ER stress agents and cell wall disturbing agents (0.075 µg/ml TM, 10 mM DTT, 5 mg/ml CR, 1.5 mg/ml CFW) and incubated at 30°C for 3.5 days. (C) Virulence analysis of ire1 strains. A/Jcr mice were infected with 105 cells of MATα WT (black square, H99), ire1 (blue diamond, YSB552), ire1+IRE1 complemented (green triangle, YSB1000) strains by intranasal inhalation. Percent survival (%) was monitored for 6 weeks post-infection. P<0.0001 for WT vs. ire1 mutant and P = 0.1001 for WT vs. ire1+IRE1 complemented strain.