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Candida glabrata  is a human commensal and an opportunistic human fungal pathogen. It is more closely related to the model yeast  Saccharomyces cerevisiae  than other  Candida spp . Compared with  S .  cerevisiae ,  C .  glabrata  exhibits higher innate tolerance to various environmental stressors, including hyperthermal stress. Here we investigate the molecular mechanisms of  C .  glabrata  adaptation to heat stress via adaptive laboratory evolution. We show that all parallel evolved populations readily adapt to hyperthermal challenge (from 47 °C to 50 °C) and exhibit convergence in evolved phenotypes with extensive cross-tolerance to various other environmental stressors such as oxidants, acids, and alcohols. Genome resequencing identified fixation of mutations in  CgSTE11  in all parallel evolved populations. The  CgSTE11  homolog in  S .  cerevisiae  plays crucial roles in various mitogen-activated protein kinase (MAPK) signaling pathways, but its role is less understood in  C .  glabrata . Subsequent verification confirmed that  CgSTE11  is important in hyperthermal tolerance and the observed extensive cross-tolerance to other environmental stressors. These results support the hypothesis that  CgSTE11  mediates cross-talks between MAPK signaling pathways in  C .  glabrata  in response to environmental challenges.

CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata