Adaptation to Environmental Stresses in Candida glabrata

Abstract

Candida glabrata (C. glabrata) is an emerging opportunistic human fungal pathogen with an increasing incidence as the cause of both mucosal and systemic infections. In addition, the fungus is the most commonly used microorganism for pyruvate production and is considered to be a potential producer of other fine chemicals and biofuels. Thus, this yeast has potential importance in both the medical and biotechnology fields. The inherent high tolerance of C. glabrata and its’ ability to readily adapt to various environmental stressors play key roles in its success as an opportunistic pathogen and potential as an industrial producer. However, the current knowledge on the underlying molecular mechanisms of C. glabtata adaptation to environmental stressors is limited. A deeper understanding of how C. glabrata adapts to environmental challenges can potentially expand our ability to combat infections involving this organism and to our toolkit for engineering better production hosts. In this dissertation, we focused on C. glabrata adaptation to two environmental stressors, hyperthermal and hydrogen peroxide. Using the strategy of adaptive laboratory evolution combined with next generation sequencing and transcriptome analyses, we begin to uncover the important genetic determinants conferring tolerance to these stressors. We showed for the first time that several genes (e.g. CAGL0B02739g and CAGL0E01243g) play important roles in cellular tolerance to selected environmental stresses (heat and H2O2) in C. glabrata; proposed potential mechanisms based on the transcriptome analyses and functions of their orthologs in the model yeast S. cerevisiae; and found that the adaptation to thermal stress in this fungus led to the acquisition of cross-tolerance to a wide range of other environmental stresses, including hydrogen peroxide, acids, and several organic solvents. Mutations in an important component of the fungal MAPK signaling cascades were shown to be responsible for the observed cross-tolerance, suggesting their critical roles in the cross-talk between different signaling pathways for cells to survive hostile environmental conditions.