CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata

Mian Huang,Katy C Kao,Julian Daniel Torres Vanega,Manpreet Kaur,Jibran Khan,Anand K Ramasubramanian,Orlando Andres Aguilar Patiño

doi:10.1038/s41598-019-53593-5

Abstract

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.

Highlights

Candida glabrata is a human commensal and an opportunistic human fungal pathogen
The results demonstrate that mutations in CgSTE11 contributed to the enhanced tolerance to various environmental stressors observed in the adaptive mutants
We identified and confirmed that mutations in CgSTE11 found in hyperthermal evolved mutants contribute to enhanced tolerance to a wide range of environmental stressors and that the mitogen-activated protein kinase (MAPK) kinase kinase likely plays a key role in cellular response to environmental stressors in C. glabrata

Summary

Introduction

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. 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. While the few existing studies have identified several cellular components involved in stress tolerance in C. glabrata based on knowledge in S. cerevisiae, the regulatory and signaling pathways involved in response to environmental stressors, including heat, are still largely unknown in this important yeast. Subsequent verification via site-directed mutagenesis confirmed that mutations in CgSTE11 played a major role in the hyperthermal tolerance and the observed cross-tolerance to other environmental stressors, providing strong evidence that CgSTE11 mediates cross-talks between MAPK signaling pathways in C. glabrata in response to environmental stressors

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Discussion

Conclusion